乳腺癌前哨淋巴结术中分子诊断及临床病理学研究
|
摘要
目前,腋窝淋巴结有无转移仍是乳腺癌患者最重要的预后判断指标。传统的方法是进行腋窝淋巴结清扫(Axillary Lymph Node Dissection,ALND)以获得腋窝淋巴结的状态,从而对乳腺癌患者进行分期和制定治疗方案。然而ALND可造成患者上肢水肿、疼痛、手臂运动功能受损和肩部僵硬等并发症,严重影响患者的生活质量,已逐渐被前哨淋巴结活检(Sentinel Lymph Node Biopsy, SLNB)所替代。许多研究表明,前哨淋巴结(Sentinel Lymph Node, SLN)可以准确地预测早期乳腺癌患者的腋窝状态。若SLN为阴性,则高度提示其他腋窝淋巴结未被累及,患者无需接受进一步的腋窝手术。这样既可以使患者避免ALND所带来的伤害,还可以减轻患者的经济负担；若SLN为阳性,可在术中即行ALND,避免二次手术。
作为一项新兴技术,SLN在乳腺癌中的应用仍存在诸多问题,如SLN术中及术后病理检测的最优方法、SLN具体的病理诊断标准、对导管原位癌(Ductal Carcinoma In Situ, DCIS)或导管原位癌伴微浸润(Ductal Carcinoma In Situ with Microinvasion, DCIS-MI)患者是否常规行SLNB、以及如何有效地预测乳腺癌是否具有高SLN转移潜能等。本课题针对以上方面展开研究与讨论,全文共分为三部分。
第一部分乳腺癌前哨淋巴结术中分子诊断临床实用性研究
目的：(1)探讨GeneSearchTM乳腺淋巴结检测试剂盒(以下简称GeneSearch)在中国人群乳腺癌患者中的临床实用性。(2)探讨One Step Nucleic Acid Amplification(一步核酸扩增法,以下简称OSNA)检测试剂盒在中国人群乳腺癌患者中的临床实用性。
方法：(1)选取复旦大学附属肿瘤医院2009年2-6月行SLNB的乳腺癌患者88例,术中送SLN分别行术中细胞印片(Intraoperative Imprint Cytology, IIC)和GeneSearch检测。以术后连续切片结果为金标准,计算GeneSearch检测方法的敏感度、特异性、阳性预测值、阴性预测值及其与连续切片结果的总体符合率,同时与术中细胞印片的结果进行比较分析,评价GeneSearch检测在中国人群乳腺癌SLN诊断中的价值。(2)选取复旦大学附属肿瘤医院2010年3-7月行SLNB的乳腺癌115例,术中送SLN分别行ⅡC和OSNA检测,以术后连续切片的结果为金标准,计算OSNA检测方法的敏感度、特异性、阳性预测值、阴性预测值及其与连续切片结果的总体符合率,同时与ⅡC的结果进行比较分析,评价OSNA检测在中国人群乳腺癌SLN术中诊断中的价值。
结果：(1)GeneSearch研究结果：①88例入组乳腺癌患者年龄28-79岁,平均年龄57岁,中位年龄60岁。6例DCIS均未发生SLN转移。12例DCIS-MI中有2例发现SLN转移,且转移类型均为宏转移。66例浸润性导管癌(Invasive Ductal Carcinoma,IDC)中18例发生SLN宏转移,4例发生微转移。1例浸润性小叶癌、2例Paget病及1例实性乳头状癌SLN均为阴性。②88例乳腺癌患者共成功检出225枚SLN,平均2.6枚/人。63例患者未发生淋巴结转移,19例患者出现SLN宏转移,4例患者为SLN微转移,2例患者SLN中出现孤立肿瘤细胞(Isolated Tumor Cells,ITCs);阴性SLN数为189枚(其中5枚为ITCs),宏转移27枚,微转移9枚；③GeneSearch结果显示阴性SLN为189枚,阳性SLN为36枚；阴性患者数65例,阳性患者数23例。GeneSearch对宏转移淋巴结的检测敏感度为96.3%(26/27),对微转移淋巴结的检测敏感度为55.6%(5/9)。对于5枚ITCs淋巴结,GeneSearch检测出2枚为阳性。④基于淋巴结数目,GeneSearch与术后连续切片的总体符合率为95.6%(215/225,95%可信区间：91.7%-97.7%),其敏感度为86.1%(31/36；95%可信区间：69.7%-94.8%),特异性为97.4%(184/189；95%可信区间：93.6%-99.0%),阳性预测值为86.1%(31/36；95%可信区间：69.7%-94.8%),阴性预测值为97.4%(184/189；95%可信区间：93.6%-99.0%)；基于患者数目,GeneSearch与术后连续切片的总体符合率为93.2%(82/88；95%可信区间：85.2%-97.2%),其敏感度为84.0%(21/25；95%可信区间：63.1%-94.7%),特异性为96.8%(61/63；95%可信区间：88.0%-99.4%),阳性预测值为91.3%(21/23；95%可信区间：70.5%-94.7%),阴性预测值为93.8%(61/65；95%可信区间：84.2%-98.0%)。无论基于淋巴结数目还是患者数目,GeneSearch的检测结果与术后连续切片结果比较均显示无统计学差异(P值分别为1.000和0.684),提示GeneSearch能达到与术后连续切片相似的诊断效果。⑤GeneSearch与术后连续切片诊断不一致淋巴结的分析显示,共10(4.4%)枚淋巴结诊断不一致。其中5(2.2%)枚为“假阳性”,其中2枚术后连续切片诊断为ITCs;5(2.2%)枚为“假阴性”,其中4枚术后连续切片诊断为微转移。⑥基于淋巴结数,GeneSearch检测方法与ⅡC总体敏感度的对比显示出统计学差异(86.1%vs72.2%,P=0.039)。⑦SLN转移类型与CK19(γ=-0.830,P=0.000)及mammaglobin (γ=-0.830,P=0.000)的Ct值存在显著负相关性,即转移灶越大相应Ct值越小。(2)OSNA研究结果：①115例入组乳腺癌患者年龄24-80岁,平均年龄50岁,中位年龄50岁。12例DCIS及11例DCIS-MI均未发生SLN转移；83例IDC中18例发生SLN宏转移,7例发生微转移；其他类型乳腺癌中仅一例黏液腺癌发现SLN宏转移。②115例乳腺癌患者共成功检出370枚SLN,平均3枚/每人。89例患者SLN阴性(其中包括1例ITCs),19例患者SLN为宏转移,7例为微转移；因59枚SLN重量<100mg未接受OSNA检测,故仅311枚SLN纳入统计。其中阴性SLN275枚(其中4枚为ITCs),宏转移25枚,微转移11枚。③OSNA结果显示24枚SLN为(++),11枚SLN为(+),4枚SLN为[+(Ⅰ)],272枚SLN为(一)。④基于淋巴结数目,OSNA法与术后连续切片的总体符合率为95.2%(296/311,95%可信区间：91.6%-96.9%),其敏感度为83.3%(30/36；95%可信区间：66.5%-93.0%),特异性为96.7%(266/275；95%可信区间：93.7%-98.4%),阳性预测值为76.9%(30/39;95%可信区间：60.3%-88.3%),阴性预测值为97.8%(266/272；95%可信区间：95.0%-99.1%)；基于患者数目,OSNA法与术后连续切片的总体符合率为87.8%(101/115；95%可信区间：80.1%-92.9%),其敏感度为80.8%(21/26；95%可信区间：60.0%-92.7%),特异性为89.9%(80/89；95%可信区间：81.2%-95.0%),阳性预测值为70.0%(21/30；95%可信区间：50.4%-84.6%),阴性预测值为94.1%(80/89；95%可信区间：86.2%-97.8%)。无论是基于淋巴结数目或是患者数目,OSNA方法的检测结果与术后连续切片结果对比均显示无统计学差异(P值分别为0.607和0.424),提示OSNA方法能达到与术后连续切片相似的诊断效果。⑤共15(4.8%)枚诊断不一致淋巴结,其中6(1.9%)枚为“假阴性”,9(2.9%)枚为“假阳性”。11枚可能是因为转移癌灶的“分布误差”所致。⑥基于淋巴结数目,OSNA检测方法与ⅡC总体敏感度的对比未显示出统计学差异(83.3%vs83.3%,P=0.267)。
结论：(1)GeneSearch用于SLN术中诊断可以达到满意的效果,并具有组织利用度高、客观、标准化、重复性高等优点,但在其临床应用中仍面临一些尚待解决的问题,有待于进一步临床研究数据的支持。(2)OSNA用于SLN术中诊断亦可达到满意的效果,也具有组织利用度高、客观、标准化、重复性高等优点,它还可以区分微转移和宏转移。但在其临床应用中仍面临一些尚待解决的问题,有待于进一步的临床研究。(3)GeneSearch与OSNA具有各自的优缺点,但均可有效地诊断SLN,可作为SLN传统病理诊断方法的有益补充。
第二部分乳腺癌导管原位中前哨淋巴结活检临床价值的研究
目的：(1)研究乳腺DCIS中SLNB的临床价值。(2)研究DCIS-MI中SLNB的临床价值。
方法：研究对象来源于复旦大学附属肿瘤医院乳腺癌SLN研究数据库(2005-2011年)。随机抽取85例DCIS及60例DCIS-MI。其中20例(8例为DCIS,12例为DCIS-MI)还进行了GeneSearch检测。评价145例DCIS和DCIS-MI患者肿瘤大小、组织学分级、临床表现、钼靶表现、是否伴有坏死、雌孕激素受体状态等临床病理参数,分析这些参数与SLN转移状态及转移类型的相关性,分析DCIS及DCIS-MI患者中SLNB的意义。
结果：(1)85例DCIS均为女性患者。发病年龄23-84岁,平均发病年龄50岁,中位发病年龄51岁。肿瘤最大径0～6cm,平均1.4cm。共成功摘取241枚SLN,平均每个患者摘除3枚SLN。仅一例(1.2%)患者显示出一枚微转移的SLN,对该患者术中行ALND,其15枚腋窝淋巴结均为阴性。另有11例患者还进行了ALND,无一例发现腋窝淋巴结转移。统计学分析未发现SLN转移的危险因素。(2)60例DCIS-MI均为女性患者。发病年龄30-81岁,平均发病年龄52岁,中位发病年龄53岁。肿瘤最大径0-5.5cm,平均2.4cm。两例患者(3.3%)发现SLN宏转移。另有两例患者的SLN发现ITCs。12例患者还进行了ALND,无一例发现腋窝淋巴结转移。统计学分析亦未发现SLN转移的危险因素。(3)GeneSearch检测结果显示8例DCIS均为阴性结果,12例DCIS-MI中有2例为阳性结果。该结果与连续切片的结果完全一致。
结论：(1)DCIS及DCIS-MI患者的淋巴结转移率很低,不建议将SLNB作为单纯DCIS患者和DCIS-MI的常规治疗方法。(2)选择性地对一些术前诊断为DCIS的患者行SLNB是必要的。但目前尚无肯定的危险因素用来指示何种术前诊断的DCIS会在术后发现浸润性癌,因此究竟选择哪些DCIS患者接受SLNB还有待我们进一步的研究。(3)对于肿块较大、组织学级别高、H&E上呈现多灶微浸润灶或出现脉管侵犯的DCIS-MI患者可能需要进行SLNB,但还需要大样本量长期随访资料的支持。(4) DCIS或DCIS-MI患者出现转移的淋巴结常为微转移或ITCs,其临床价值还有待进一步的研究。
第三部分乳腺癌中aB-晶体蛋白、半乳凝素-7的表达及其与前哨淋巴结转移的相关性研究
目的：通过检测各种SLN转移类型乳腺癌原发灶及SLN转移灶中αB-晶体蛋白(aB-crystallin)及半乳凝素-7(Galectin-7)的表达,分析两者与乳腺癌SLN转移的相关性。
方法：收集复旦大学附属肿瘤医院2005-2009年具有完整临床病理资料及随访资料的乳腺癌患者174例,所有患者均行SLNB,组织学类型均为浸润性导管癌,非特殊类型。收集其乳腺癌原发灶的石蜡包埋组织、相应正常乳腺石蜡包埋组织及宏转移病例SLN石蜡包埋组织；将石蜡包埋组织制作成组织芯片,免疫组化检测aB-crystallin及Galectin-7的表达。
结果：(1)174例乳腺癌均为女性患者,发病年龄28-85岁,平均发病年龄51岁,中位发病年龄51岁。肿瘤最大径0-5.5cm,平均2.2cm。174例患者共摘取484枚SLNs,平均每个患者摘除3枚SLN。其中,宏转移组患者96例,微转移组患者23例,无转移组患者55例(其中包括5例ITCs)。(2) aB-crystallin的表达情况：①96例宏转移患者中共59例(61.4%)为阳性表达。23例微转移患者中8(34.8%)例显示为弱阳性。无转移组中12例(21.8%)显示为弱阳性；②转移(包括宏转移和微转移)组aB-crystallin的阳性率显著高于无转移组(x2=18.045,P=0.000)。宏转移组aB-crystallin的阳性率显著高于无转移组(x2=22.056,P=0.000)；随着乳腺癌组织学级别的升高,aB-crystallin蛋白的阳性率也逐步升高,结果具有统计学意义(x2=7.306,P=0.026)。③68例宏转移病例的SLN转移癌排入组织芯片。aB-crystallin蛋白在转移灶的阳性率显著高于原发灶(86.8%vs61.4%,x2=12.631,P=0.000)。(3)Galectin-7的表达情况：①三类不同SLN转移类型组间Galectin-7的胞质阳性率未显示出明显的差异(x2=2.398,P=0.301),而Galectin-7的核阳性率显著不同。转移(包括宏转移和微转移)组Galectin-7的核阳性率显著低于无转移组(x2=6.959,P=0.008)。分层统计显示宏转移组Galectin-7核阳性率显著低于无转移组(x2=8.882,P=0.030)。②随着乳腺癌组织学级别的升高,Galectin-7的核阳性率在逐步降低,结果具有统计学意义(x2=16.732,P=0.000)。③HER2过表达组及三阴性组的Galectin-7核阳性率低于腔面A型和腔面B型组。④共68例宏转移病例的SLN转移癌排入组织芯片。Galectin-7蛋白在SLN转移灶中胞质表达的阳性强度显著高于乳腺癌原发灶(强阳性病例：54.4%vs35.4%,x2=9.433,P=0.007,精确概率法)。Galectin-7核阳性率显著低于相应宏转移组原发癌的核阳性率(17.6%vs45.8%,x2=14.063,P=0.000)。
结论：(1)aB-crystallin在乳腺癌转移组肿瘤原发灶的阳性率显著高于无转移组,而宏转移组SLN转移灶aB-crystallin的阳性率又显著高于原发灶的阳性率,说明aB-crystallin在乳腺癌淋巴结转移中发挥了积极的作用,可作为临床判断乳腺癌恶性程度、转移和预后的重要参考指标。(2)随着乳腺癌组织学级别的升高,aB-crystallin的阳性率也逐步升高。而随着组织学级别的升高,本组病例又显示出SLN的阳性率随之升高的趋势,由此也说明aB-crystallin的高表达可能与乳腺癌淋巴结转移相关。(3)Galectin-7在各转移类型组之间的胞质阳性率未显示出明显的差异表达,而其核是否阳性对淋巴结转移具有提示意义。转移组Galectin-7的核阳性率显著低于无转移组,分层统计宏转移组Galectin-7的核阳性显著低于为无转移组。在宏转移组,其SLN转移癌的核阳性率又显著低于相应原发癌灶。说明早期核内表达的Galectin-7可能是乳腺癌进展的负性调控因子,而Galectin-7核表达的下调很可能是乳腺癌进展的标志。
Axillary lymph node metastasis is the most important prognostic factor of breast cancer patients. Traditionally, surgeons perform axillary lymph node dissection (ALND) to identify the axillary lymph node status to provide staging information and therefore determine the treatment strategy. However, ALND can cause some complications, such as upper limb lymphedema, pain, numbness, impaired shoulder function, and stiffness. Thus, ALND has been gradually replaced by sentinel lymph node biopsy (SLNB). Many studies have shown that a sentinel lymph node (SLN) can accurately predict the status of axillary lymph nodes in early-stage breast cancer patients. If the intraoperative SLNB result is negative, it is highly suggestive that other axillary lymph nodes are not involved, and the patient does not need a further ALND. This alternative will enable the breast cancer patients to avoid the pain caused by the ALND and reduce their financial burden. If the result is positive, an ALND can be immediately performed to avoid a second surgery.
As an innovative technique, the application of SLNB in breast cancer still faces some problems, such as the optimal method for intraoperative and postoperative pathological examination of SLN, the pathological evaluation criteria of SLN, whether a routine SLNB should be carried out for patients with ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCIS-MI), as well as how to effectively predict the risk of SLN metastases in breast cancers. To illustrate the above-mentioned problems, we undertook a series of research. The current research project is comprised of the following three parts:
Part I Evaluation of intraoperative molecular assays for detecting breast cancer metastases in SLNs
Objective:(1) To investigate the clinical validation of GeneSearchTM breast lymph node assay (Veridex, ILC, Warren, NJ, USA, GeneSearch for short) for intraoperative diagnosis of metastases in SLNs of breast cancer, and compared the GeneSearch results with intraoperative imprint cytology (ⅡC) and postoperative serial sectioning.(2) To investigate the clinical validation of One-step nucleic amplification assay (OSNA for short), and compared the OSNA results with ⅡC and postoperative serial sectioning.
Methods:(1) GeneSearch study:A prospective study of229consecutive SLNs from88patients was conducted in our institution. Every SLN was cut into2mm slabs which were examined by IIC firstly, then alternatively by GeneSearch or postoperative serial sectioning. GeneSearch uses Real-time fluorescence quantitative RT-PCR to detect the expression of CK19and mammaglobin of SLNs. The results of GeneSearch were compared with the results of ⅡC and postoperative serial sectioning.(2) OSNA study:A prospective study of370consecutive SLNs from115patients was conducted in our institution. A total of311SLNs has undergone the OSAN test. All SLNs were sectioned in about2mm pieces. ⅡC was performed on all pieces, and then OSNA and postoperative serial sectioning were performed on alternative node pieces. OSNA uses loop-mediated isothermal amplification technology without the extraction of RNA from genomic DNA and contains six primers to detect the expression of CK19mRNA. The results of OSNA were compared with the results of ⅡC and postoperative serial sectioning.
Results:(1) GeneSearch study results:A total of88breast cancer patients with225SLNs (mean2.6SLNs per patient) were enrolled in the GeneSearch study. All patients but one were female, with a median age of60years (range,28-79years). Nineteen patients contained macrometastases. Four patients were diagnosed as micrometastases. Eighty-eight patients were free of metastases; Twenty-seven SLNs were identified as macrometastases. Micrometastases were found in9nodes. The other189SLNs were free of metastases, including5isolated tumor cells (ITCs). The overall rate of agreement between GeneSearch and the postoperative serial sectioning was95.6%(95%confidence interval [CI]:91.7%～97.7%), with a sensitivity of86.1%(95%CI:69.7%～94.8%) and a specificity of97.4%(95%CI:93.6%～99.0%) based on the number of SLNs. And the positive predictive value (PPV) and negative predictive value (NPV) of GeneSearch were of86.1%(95%CI:69.7%～94.8%) and97.4%(95%CI:93.6%～99.0%) respectively. Positive SLN metastasis size was correlated with the RT-PCR cycle threshold (Ct value).(2) OSNA study results:A total of115patients with370SLNs (mean3SLNs per patient) were enrolled in the OSNA study. All patients were female, with a median age of50years (range,24～80years). Nineteen patients contained macrometastases. Seven patients harbored micrometastases. Eighty-nine patients were free of metastases; Twenty-five of the370SLNs were identified as macrometastases. Micrometastases were found in11nodes. Four SLNs harbored ITCs. The other271SLNs were free of metastases. Fifty-nine nodes were too small to be sampled for the OSNA test. The overall rate of agreement between OSNA assay and the postoperative serial sectioning was95.2%(95%confidence interval [CI]:91.6～96.9%), with a sensitivity of83.3%(95%CI:66.5～93.0%), a specificity of96.7%(95%CI:93.7～98.4%), a PPV of76.9%(95%CI:60.3～88.3%), a NPV of97.8%(95%CI:95.0～99.1%) based on the number of SLNs sampled. Eleven out of15discordant SLNs can be explained by "tissue allocation bias".
Conclusions:(1) GeneSearch assay is standardized, objective, and reproducible and can utilize more lymphoid tissue. The performance of GeneSearch test for intraoperative diagnosis of SLNs is equivalent to the postoperative serial sectioning. GeneSearch can obtain a relatively higher sensitivity than IIC, especially for the micrometastases SLNs. We recommend GeneSearch be used in daily clinical diagnostic work.(2) OSNA assay is also standardized, objective, and reproducible and can utilize more lymphoid tissue. In addition, it can distinguish between micrometastasis and macrometastasis to enable us to make further study of the significance of micrometastasis. The performance of OSNA assay for intraoperative diagnosis of SLNs is equivalent to the postoperative serial sectioning. We recommend that OSNA assay can be used in daily clinical diagnostic work.(3) Although GeneSearch and OSNA have their own advantages and disadvantages, both of them can provide a good performance; and therefore can be good alternative methods for traditional pathological diagnosis.
Part II SLNB in Patients with DCIS and DCIS-MI
Objective:The role of SLNB in DCIS or DCIS-MI is still in controversy. The purpose of our study is to determine if there is a need for SLNB in patients with pure DCIS or DCIS-MI.
Methods:One hundred and forty five patients with DCIS or DCIS-MI who underwent SLNB between March2009and March2011at the Fudan University Shanghai Cancer Center (FUSCC) were enrolled in our cohort. There were85patients with DCIS and60patients with DCIS-MI,20patients (8DCIS,12DCIS-MI) of whom were also tested by the GeneSearch Assay. The clinicopathological parameters such as the tumor size, histological grade, clinical presentation, mammographic manifestation, necrosis, and the status of ER and PR were summarized. The correlation between these parameters and SLN metastasis was analyzed. We also evaluated whether SLNB is required in patients with DCIS or DCIS-MI.
Results:(1) Clinical features of DCIS patients:All patients were female. The ages ranged from23to84years (mean50years, median51years). The tumor size ranged from0to6cm, with a mean of1.4cm. A total of241SLNs was successfully detected with an average of3SLNs per patient. Only one (1.2%) patient showed a micrometastatic SLN. Twelve patients also underwent an ALND. None was demonstrated a metastasis. Statistical analysis showed no identified risk factors of SLN metastasis.(2) Clinical features of DCIS-MI patients:All patients were female. The ages ranged from30to81years (mean52years, median53years). The tumor size ranged from0to5.5cm, with a mean of2.4cm. A total of171SLNs was successfully detected with an average of3per patient. Two patients (2/60,3.3%) were detected to have macrometastatic SLNs. In addition, two cases displayed ITCs. Twelve patients also undergone ALND and none of them showed a positive lymph node. Statistical analysis displayed no risk factors of SLN metastasis.(3) GeneSearch Assay results:None of the8DCIS patients showed a positive result. In12DCIS-MIs,2patients were positive. The results were fully consistent with the results of serial sectioning.
Conclusions:(1) Based on our currently available data, the routine use of SLNB in all patients with DCIS or DCIS-MI is not warranted. It is necessary to select certain kind of patients initially diagnosed with DCIS to undergo SLNB. However, it is also acknowledged that there are still no definite risk factors used to indicate an invasive component will be found after surgery.(2) Selected DCIS-MI patients with large tumor, high grade, several invasive clusters and vascular invasion seem to need a concomitant SLNB. Nevertheless, this should be certified by further investigation with larger numbers of patients and long follow-up.(3) Most of the SLN-positive DCIS or DCIS-MI patients were micrometastases or ITCs whose clinical significance and prognostic implications is still in controversy.
Part Ⅲ Expressions and significance of aB-crystallin and Galectin-7in breast cancer with different metastatic types of SLN
Objective:The purpose of the study is to use aB-crystallin and Galectin-7to detect the expression in breast cancers with different metastatic types of SLN, and to explore their significance.
Methods:One hundred and seventy four patients with IDC not otherwise specified who underwent SLNB between2005and March2009at FUSCC were enrolled in our cohort. The paraffin-embedded tissue samples of the primary breast cancer, the corresponding normal breast and the SLNs of macrometastatic cases were collected and included in tissue microarrays (TMAs), and stained with antibodies against aB-crystallin and Galectin-7.
Results:(1) All patients were female. The ages ranged from28to85years (mean51years, median51years). The tumor size ranged from0to5.5cm, with a mean of2.2cm. A total of484SLNs was successfully detected with an average of3SLNs per patient. Among these174patients,96cases were diagnosed as macrometastases,23cases were micrometastases, and the other55cases were free of metastasis (including5ITCs).(2) Expression of aB-crystallin:Fifty-nine out of the96(61.4%) macrometastatic cases were positive for aB-crystallin. Eight out of the23(34.8%) micrometastatic cases were positive for aB-crystallin. Twelve out of the55(21.8%) SLN-negative cases were positive for aB-crystallin. In the metastasis group (including macrometastasis and micrometastasis), the expression of aB-crystallin was significantly higher than the non-metastasis group{χ2=18.045, P=0.000). The expression of aB-crystallin in macrometastasis group was statistically higher than the non-metastasis group (χ2=22.056, P=0.000). The SLN-metastatic tumors showed a significantly increased aB-crystallin protein-positive rate than the primary tumors (86.8%vs61.4%, χ2=12.631, P=0.000). Our study also revealed that aB-crystallin protein levels were gradually and significantly elevated with the increase of histological grade (χ2=7.306, P=0.026).(3) Expression of Galectin-7:Although there was no obvious difference in the cytoplasmic Galectin-7expressions among the three different metastasis groups (χ2=2.398,P=0.301), a significantly different nuclear-positive rate can be observed. In the metastasis group (including macrometastasis and micrometastasis), the nuclear-positive rate of Galectin was significantly lower than the non-metastasis group (χ2=18.045, P=0.000). The nuclear expression of Galectin-7in macrometastasis group was statistically lower than the non-metastasis group (χ2=6.959, P=0.008). The SLN-metastatic tumors showed a significantly decreased Galectin-7nuclear-positive rate than the primary tumors (17.6%vs45.8%, χ2=14.063, P=0.000), while the SLN-metastatic tumors showed a significantly increased Galectin-7cytoplasm-positive rate than the primary tumors (strong positive cases:54.4%vs35.4%, χ2=9.433, P=0.007). The nuclear expression of Galectin-7levels were gradually and significantly decreased with the increase of histological grade (χ2=16.732, P=0.000). In HER2overexpressing and triple-negative groups, the nuclear-positive rate of Galectin-7is lower than luminal A or luminal B group.
Conclusions:The expression of aB-crystallin may play an active role in the metastasis of breast cancer, and might be served as an important parameter for determining tumor biological behavior. The early nuclear expression of Galectin-7may be a negative regulatory factor in breast cancer development, while the gradual disappearance of Galectin-7nuclear expression is likely to be a sign of breast cancer progression.
作为一项新兴技术,SLN在乳腺癌中的应用仍存在诸多问题,如SLN术中及术后病理检测的最优方法、SLN具体的病理诊断标准、对导管原位癌(Ductal Carcinoma In Situ, DCIS)或导管原位癌伴微浸润(Ductal Carcinoma In Situ with Microinvasion, DCIS-MI)患者是否常规行SLNB、以及如何有效地预测乳腺癌是否具有高SLN转移潜能等。本课题针对以上方面展开研究与讨论,全文共分为三部分。
第一部分乳腺癌前哨淋巴结术中分子诊断临床实用性研究
目的：(1)探讨GeneSearchTM乳腺淋巴结检测试剂盒(以下简称GeneSearch)在中国人群乳腺癌患者中的临床实用性。(2)探讨One Step Nucleic Acid Amplification(一步核酸扩增法,以下简称OSNA)检测试剂盒在中国人群乳腺癌患者中的临床实用性。
方法：(1)选取复旦大学附属肿瘤医院2009年2-6月行SLNB的乳腺癌患者88例,术中送SLN分别行术中细胞印片(Intraoperative Imprint Cytology, IIC)和GeneSearch检测。以术后连续切片结果为金标准,计算GeneSearch检测方法的敏感度、特异性、阳性预测值、阴性预测值及其与连续切片结果的总体符合率,同时与术中细胞印片的结果进行比较分析,评价GeneSearch检测在中国人群乳腺癌SLN诊断中的价值。(2)选取复旦大学附属肿瘤医院2010年3-7月行SLNB的乳腺癌115例,术中送SLN分别行ⅡC和OSNA检测,以术后连续切片的结果为金标准,计算OSNA检测方法的敏感度、特异性、阳性预测值、阴性预测值及其与连续切片结果的总体符合率,同时与ⅡC的结果进行比较分析,评价OSNA检测在中国人群乳腺癌SLN术中诊断中的价值。
结果：(1)GeneSearch研究结果：①88例入组乳腺癌患者年龄28-79岁,平均年龄57岁,中位年龄60岁。6例DCIS均未发生SLN转移。12例DCIS-MI中有2例发现SLN转移,且转移类型均为宏转移。66例浸润性导管癌(Invasive Ductal Carcinoma,IDC)中18例发生SLN宏转移,4例发生微转移。1例浸润性小叶癌、2例Paget病及1例实性乳头状癌SLN均为阴性。②88例乳腺癌患者共成功检出225枚SLN,平均2.6枚/人。63例患者未发生淋巴结转移,19例患者出现SLN宏转移,4例患者为SLN微转移,2例患者SLN中出现孤立肿瘤细胞(Isolated Tumor Cells,ITCs);阴性SLN数为189枚(其中5枚为ITCs),宏转移27枚,微转移9枚；③GeneSearch结果显示阴性SLN为189枚,阳性SLN为36枚；阴性患者数65例,阳性患者数23例。GeneSearch对宏转移淋巴结的检测敏感度为96.3%(26/27),对微转移淋巴结的检测敏感度为55.6%(5/9)。对于5枚ITCs淋巴结,GeneSearch检测出2枚为阳性。④基于淋巴结数目,GeneSearch与术后连续切片的总体符合率为95.6%(215/225,95%可信区间：91.7%-97.7%),其敏感度为86.1%(31/36；95%可信区间：69.7%-94.8%),特异性为97.4%(184/189；95%可信区间：93.6%-99.0%),阳性预测值为86.1%(31/36；95%可信区间：69.7%-94.8%),阴性预测值为97.4%(184/189；95%可信区间：93.6%-99.0%)；基于患者数目,GeneSearch与术后连续切片的总体符合率为93.2%(82/88；95%可信区间：85.2%-97.2%),其敏感度为84.0%(21/25；95%可信区间：63.1%-94.7%),特异性为96.8%(61/63；95%可信区间：88.0%-99.4%),阳性预测值为91.3%(21/23；95%可信区间：70.5%-94.7%),阴性预测值为93.8%(61/65；95%可信区间：84.2%-98.0%)。无论基于淋巴结数目还是患者数目,GeneSearch的检测结果与术后连续切片结果比较均显示无统计学差异(P值分别为1.000和0.684),提示GeneSearch能达到与术后连续切片相似的诊断效果。⑤GeneSearch与术后连续切片诊断不一致淋巴结的分析显示,共10(4.4%)枚淋巴结诊断不一致。其中5(2.2%)枚为“假阳性”,其中2枚术后连续切片诊断为ITCs;5(2.2%)枚为“假阴性”,其中4枚术后连续切片诊断为微转移。⑥基于淋巴结数,GeneSearch检测方法与ⅡC总体敏感度的对比显示出统计学差异(86.1%vs72.2%,P=0.039)。⑦SLN转移类型与CK19(γ=-0.830,P=0.000)及mammaglobin (γ=-0.830,P=0.000)的Ct值存在显著负相关性,即转移灶越大相应Ct值越小。(2)OSNA研究结果：①115例入组乳腺癌患者年龄24-80岁,平均年龄50岁,中位年龄50岁。12例DCIS及11例DCIS-MI均未发生SLN转移；83例IDC中18例发生SLN宏转移,7例发生微转移；其他类型乳腺癌中仅一例黏液腺癌发现SLN宏转移。②115例乳腺癌患者共成功检出370枚SLN,平均3枚/每人。89例患者SLN阴性(其中包括1例ITCs),19例患者SLN为宏转移,7例为微转移；因59枚SLN重量<100mg未接受OSNA检测,故仅311枚SLN纳入统计。其中阴性SLN275枚(其中4枚为ITCs),宏转移25枚,微转移11枚。③OSNA结果显示24枚SLN为(++),11枚SLN为(+),4枚SLN为[+(Ⅰ)],272枚SLN为(一)。④基于淋巴结数目,OSNA法与术后连续切片的总体符合率为95.2%(296/311,95%可信区间：91.6%-96.9%),其敏感度为83.3%(30/36；95%可信区间：66.5%-93.0%),特异性为96.7%(266/275；95%可信区间：93.7%-98.4%),阳性预测值为76.9%(30/39;95%可信区间：60.3%-88.3%),阴性预测值为97.8%(266/272；95%可信区间：95.0%-99.1%)；基于患者数目,OSNA法与术后连续切片的总体符合率为87.8%(101/115；95%可信区间：80.1%-92.9%),其敏感度为80.8%(21/26；95%可信区间：60.0%-92.7%),特异性为89.9%(80/89；95%可信区间：81.2%-95.0%),阳性预测值为70.0%(21/30；95%可信区间：50.4%-84.6%),阴性预测值为94.1%(80/89；95%可信区间：86.2%-97.8%)。无论是基于淋巴结数目或是患者数目,OSNA方法的检测结果与术后连续切片结果对比均显示无统计学差异(P值分别为0.607和0.424),提示OSNA方法能达到与术后连续切片相似的诊断效果。⑤共15(4.8%)枚诊断不一致淋巴结,其中6(1.9%)枚为“假阴性”,9(2.9%)枚为“假阳性”。11枚可能是因为转移癌灶的“分布误差”所致。⑥基于淋巴结数目,OSNA检测方法与ⅡC总体敏感度的对比未显示出统计学差异(83.3%vs83.3%,P=0.267)。
结论：(1)GeneSearch用于SLN术中诊断可以达到满意的效果,并具有组织利用度高、客观、标准化、重复性高等优点,但在其临床应用中仍面临一些尚待解决的问题,有待于进一步临床研究数据的支持。(2)OSNA用于SLN术中诊断亦可达到满意的效果,也具有组织利用度高、客观、标准化、重复性高等优点,它还可以区分微转移和宏转移。但在其临床应用中仍面临一些尚待解决的问题,有待于进一步的临床研究。(3)GeneSearch与OSNA具有各自的优缺点,但均可有效地诊断SLN,可作为SLN传统病理诊断方法的有益补充。
第二部分乳腺癌导管原位中前哨淋巴结活检临床价值的研究
目的：(1)研究乳腺DCIS中SLNB的临床价值。(2)研究DCIS-MI中SLNB的临床价值。
方法：研究对象来源于复旦大学附属肿瘤医院乳腺癌SLN研究数据库(2005-2011年)。随机抽取85例DCIS及60例DCIS-MI。其中20例(8例为DCIS,12例为DCIS-MI)还进行了GeneSearch检测。评价145例DCIS和DCIS-MI患者肿瘤大小、组织学分级、临床表现、钼靶表现、是否伴有坏死、雌孕激素受体状态等临床病理参数,分析这些参数与SLN转移状态及转移类型的相关性,分析DCIS及DCIS-MI患者中SLNB的意义。
结果：(1)85例DCIS均为女性患者。发病年龄23-84岁,平均发病年龄50岁,中位发病年龄51岁。肿瘤最大径0～6cm,平均1.4cm。共成功摘取241枚SLN,平均每个患者摘除3枚SLN。仅一例(1.2%)患者显示出一枚微转移的SLN,对该患者术中行ALND,其15枚腋窝淋巴结均为阴性。另有11例患者还进行了ALND,无一例发现腋窝淋巴结转移。统计学分析未发现SLN转移的危险因素。(2)60例DCIS-MI均为女性患者。发病年龄30-81岁,平均发病年龄52岁,中位发病年龄53岁。肿瘤最大径0-5.5cm,平均2.4cm。两例患者(3.3%)发现SLN宏转移。另有两例患者的SLN发现ITCs。12例患者还进行了ALND,无一例发现腋窝淋巴结转移。统计学分析亦未发现SLN转移的危险因素。(3)GeneSearch检测结果显示8例DCIS均为阴性结果,12例DCIS-MI中有2例为阳性结果。该结果与连续切片的结果完全一致。
结论：(1)DCIS及DCIS-MI患者的淋巴结转移率很低,不建议将SLNB作为单纯DCIS患者和DCIS-MI的常规治疗方法。(2)选择性地对一些术前诊断为DCIS的患者行SLNB是必要的。但目前尚无肯定的危险因素用来指示何种术前诊断的DCIS会在术后发现浸润性癌,因此究竟选择哪些DCIS患者接受SLNB还有待我们进一步的研究。(3)对于肿块较大、组织学级别高、H&E上呈现多灶微浸润灶或出现脉管侵犯的DCIS-MI患者可能需要进行SLNB,但还需要大样本量长期随访资料的支持。(4) DCIS或DCIS-MI患者出现转移的淋巴结常为微转移或ITCs,其临床价值还有待进一步的研究。
第三部分乳腺癌中aB-晶体蛋白、半乳凝素-7的表达及其与前哨淋巴结转移的相关性研究
目的：通过检测各种SLN转移类型乳腺癌原发灶及SLN转移灶中αB-晶体蛋白(aB-crystallin)及半乳凝素-7(Galectin-7)的表达,分析两者与乳腺癌SLN转移的相关性。
方法：收集复旦大学附属肿瘤医院2005-2009年具有完整临床病理资料及随访资料的乳腺癌患者174例,所有患者均行SLNB,组织学类型均为浸润性导管癌,非特殊类型。收集其乳腺癌原发灶的石蜡包埋组织、相应正常乳腺石蜡包埋组织及宏转移病例SLN石蜡包埋组织；将石蜡包埋组织制作成组织芯片,免疫组化检测aB-crystallin及Galectin-7的表达。
结果：(1)174例乳腺癌均为女性患者,发病年龄28-85岁,平均发病年龄51岁,中位发病年龄51岁。肿瘤最大径0-5.5cm,平均2.2cm。174例患者共摘取484枚SLNs,平均每个患者摘除3枚SLN。其中,宏转移组患者96例,微转移组患者23例,无转移组患者55例(其中包括5例ITCs)。(2) aB-crystallin的表达情况：①96例宏转移患者中共59例(61.4%)为阳性表达。23例微转移患者中8(34.8%)例显示为弱阳性。无转移组中12例(21.8%)显示为弱阳性；②转移(包括宏转移和微转移)组aB-crystallin的阳性率显著高于无转移组(x2=18.045,P=0.000)。宏转移组aB-crystallin的阳性率显著高于无转移组(x2=22.056,P=0.000)；随着乳腺癌组织学级别的升高,aB-crystallin蛋白的阳性率也逐步升高,结果具有统计学意义(x2=7.306,P=0.026)。③68例宏转移病例的SLN转移癌排入组织芯片。aB-crystallin蛋白在转移灶的阳性率显著高于原发灶(86.8%vs61.4%,x2=12.631,P=0.000)。(3)Galectin-7的表达情况：①三类不同SLN转移类型组间Galectin-7的胞质阳性率未显示出明显的差异(x2=2.398,P=0.301),而Galectin-7的核阳性率显著不同。转移(包括宏转移和微转移)组Galectin-7的核阳性率显著低于无转移组(x2=6.959,P=0.008)。分层统计显示宏转移组Galectin-7核阳性率显著低于无转移组(x2=8.882,P=0.030)。②随着乳腺癌组织学级别的升高,Galectin-7的核阳性率在逐步降低,结果具有统计学意义(x2=16.732,P=0.000)。③HER2过表达组及三阴性组的Galectin-7核阳性率低于腔面A型和腔面B型组。④共68例宏转移病例的SLN转移癌排入组织芯片。Galectin-7蛋白在SLN转移灶中胞质表达的阳性强度显著高于乳腺癌原发灶(强阳性病例：54.4%vs35.4%,x2=9.433,P=0.007,精确概率法)。Galectin-7核阳性率显著低于相应宏转移组原发癌的核阳性率(17.6%vs45.8%,x2=14.063,P=0.000)。
结论：(1)aB-crystallin在乳腺癌转移组肿瘤原发灶的阳性率显著高于无转移组,而宏转移组SLN转移灶aB-crystallin的阳性率又显著高于原发灶的阳性率,说明aB-crystallin在乳腺癌淋巴结转移中发挥了积极的作用,可作为临床判断乳腺癌恶性程度、转移和预后的重要参考指标。(2)随着乳腺癌组织学级别的升高,aB-crystallin的阳性率也逐步升高。而随着组织学级别的升高,本组病例又显示出SLN的阳性率随之升高的趋势,由此也说明aB-crystallin的高表达可能与乳腺癌淋巴结转移相关。(3)Galectin-7在各转移类型组之间的胞质阳性率未显示出明显的差异表达,而其核是否阳性对淋巴结转移具有提示意义。转移组Galectin-7的核阳性率显著低于无转移组,分层统计宏转移组Galectin-7的核阳性显著低于为无转移组。在宏转移组,其SLN转移癌的核阳性率又显著低于相应原发癌灶。说明早期核内表达的Galectin-7可能是乳腺癌进展的负性调控因子,而Galectin-7核表达的下调很可能是乳腺癌进展的标志。
Axillary lymph node metastasis is the most important prognostic factor of breast cancer patients. Traditionally, surgeons perform axillary lymph node dissection (ALND) to identify the axillary lymph node status to provide staging information and therefore determine the treatment strategy. However, ALND can cause some complications, such as upper limb lymphedema, pain, numbness, impaired shoulder function, and stiffness. Thus, ALND has been gradually replaced by sentinel lymph node biopsy (SLNB). Many studies have shown that a sentinel lymph node (SLN) can accurately predict the status of axillary lymph nodes in early-stage breast cancer patients. If the intraoperative SLNB result is negative, it is highly suggestive that other axillary lymph nodes are not involved, and the patient does not need a further ALND. This alternative will enable the breast cancer patients to avoid the pain caused by the ALND and reduce their financial burden. If the result is positive, an ALND can be immediately performed to avoid a second surgery.
As an innovative technique, the application of SLNB in breast cancer still faces some problems, such as the optimal method for intraoperative and postoperative pathological examination of SLN, the pathological evaluation criteria of SLN, whether a routine SLNB should be carried out for patients with ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCIS-MI), as well as how to effectively predict the risk of SLN metastases in breast cancers. To illustrate the above-mentioned problems, we undertook a series of research. The current research project is comprised of the following three parts:
Part I Evaluation of intraoperative molecular assays for detecting breast cancer metastases in SLNs
Objective:(1) To investigate the clinical validation of GeneSearchTM breast lymph node assay (Veridex, ILC, Warren, NJ, USA, GeneSearch for short) for intraoperative diagnosis of metastases in SLNs of breast cancer, and compared the GeneSearch results with intraoperative imprint cytology (ⅡC) and postoperative serial sectioning.(2) To investigate the clinical validation of One-step nucleic amplification assay (OSNA for short), and compared the OSNA results with ⅡC and postoperative serial sectioning.
Methods:(1) GeneSearch study:A prospective study of229consecutive SLNs from88patients was conducted in our institution. Every SLN was cut into2mm slabs which were examined by IIC firstly, then alternatively by GeneSearch or postoperative serial sectioning. GeneSearch uses Real-time fluorescence quantitative RT-PCR to detect the expression of CK19and mammaglobin of SLNs. The results of GeneSearch were compared with the results of ⅡC and postoperative serial sectioning.(2) OSNA study:A prospective study of370consecutive SLNs from115patients was conducted in our institution. A total of311SLNs has undergone the OSAN test. All SLNs were sectioned in about2mm pieces. ⅡC was performed on all pieces, and then OSNA and postoperative serial sectioning were performed on alternative node pieces. OSNA uses loop-mediated isothermal amplification technology without the extraction of RNA from genomic DNA and contains six primers to detect the expression of CK19mRNA. The results of OSNA were compared with the results of ⅡC and postoperative serial sectioning.
Results:(1) GeneSearch study results:A total of88breast cancer patients with225SLNs (mean2.6SLNs per patient) were enrolled in the GeneSearch study. All patients but one were female, with a median age of60years (range,28-79years). Nineteen patients contained macrometastases. Four patients were diagnosed as micrometastases. Eighty-eight patients were free of metastases; Twenty-seven SLNs were identified as macrometastases. Micrometastases were found in9nodes. The other189SLNs were free of metastases, including5isolated tumor cells (ITCs). The overall rate of agreement between GeneSearch and the postoperative serial sectioning was95.6%(95%confidence interval [CI]:91.7%～97.7%), with a sensitivity of86.1%(95%CI:69.7%～94.8%) and a specificity of97.4%(95%CI:93.6%～99.0%) based on the number of SLNs. And the positive predictive value (PPV) and negative predictive value (NPV) of GeneSearch were of86.1%(95%CI:69.7%～94.8%) and97.4%(95%CI:93.6%～99.0%) respectively. Positive SLN metastasis size was correlated with the RT-PCR cycle threshold (Ct value).(2) OSNA study results:A total of115patients with370SLNs (mean3SLNs per patient) were enrolled in the OSNA study. All patients were female, with a median age of50years (range,24～80years). Nineteen patients contained macrometastases. Seven patients harbored micrometastases. Eighty-nine patients were free of metastases; Twenty-five of the370SLNs were identified as macrometastases. Micrometastases were found in11nodes. Four SLNs harbored ITCs. The other271SLNs were free of metastases. Fifty-nine nodes were too small to be sampled for the OSNA test. The overall rate of agreement between OSNA assay and the postoperative serial sectioning was95.2%(95%confidence interval [CI]:91.6～96.9%), with a sensitivity of83.3%(95%CI:66.5～93.0%), a specificity of96.7%(95%CI:93.7～98.4%), a PPV of76.9%(95%CI:60.3～88.3%), a NPV of97.8%(95%CI:95.0～99.1%) based on the number of SLNs sampled. Eleven out of15discordant SLNs can be explained by "tissue allocation bias".
Conclusions:(1) GeneSearch assay is standardized, objective, and reproducible and can utilize more lymphoid tissue. The performance of GeneSearch test for intraoperative diagnosis of SLNs is equivalent to the postoperative serial sectioning. GeneSearch can obtain a relatively higher sensitivity than IIC, especially for the micrometastases SLNs. We recommend GeneSearch be used in daily clinical diagnostic work.(2) OSNA assay is also standardized, objective, and reproducible and can utilize more lymphoid tissue. In addition, it can distinguish between micrometastasis and macrometastasis to enable us to make further study of the significance of micrometastasis. The performance of OSNA assay for intraoperative diagnosis of SLNs is equivalent to the postoperative serial sectioning. We recommend that OSNA assay can be used in daily clinical diagnostic work.(3) Although GeneSearch and OSNA have their own advantages and disadvantages, both of them can provide a good performance; and therefore can be good alternative methods for traditional pathological diagnosis.
Part II SLNB in Patients with DCIS and DCIS-MI
Objective:The role of SLNB in DCIS or DCIS-MI is still in controversy. The purpose of our study is to determine if there is a need for SLNB in patients with pure DCIS or DCIS-MI.
Methods:One hundred and forty five patients with DCIS or DCIS-MI who underwent SLNB between March2009and March2011at the Fudan University Shanghai Cancer Center (FUSCC) were enrolled in our cohort. There were85patients with DCIS and60patients with DCIS-MI,20patients (8DCIS,12DCIS-MI) of whom were also tested by the GeneSearch Assay. The clinicopathological parameters such as the tumor size, histological grade, clinical presentation, mammographic manifestation, necrosis, and the status of ER and PR were summarized. The correlation between these parameters and SLN metastasis was analyzed. We also evaluated whether SLNB is required in patients with DCIS or DCIS-MI.
Results:(1) Clinical features of DCIS patients:All patients were female. The ages ranged from23to84years (mean50years, median51years). The tumor size ranged from0to6cm, with a mean of1.4cm. A total of241SLNs was successfully detected with an average of3SLNs per patient. Only one (1.2%) patient showed a micrometastatic SLN. Twelve patients also underwent an ALND. None was demonstrated a metastasis. Statistical analysis showed no identified risk factors of SLN metastasis.(2) Clinical features of DCIS-MI patients:All patients were female. The ages ranged from30to81years (mean52years, median53years). The tumor size ranged from0to5.5cm, with a mean of2.4cm. A total of171SLNs was successfully detected with an average of3per patient. Two patients (2/60,3.3%) were detected to have macrometastatic SLNs. In addition, two cases displayed ITCs. Twelve patients also undergone ALND and none of them showed a positive lymph node. Statistical analysis displayed no risk factors of SLN metastasis.(3) GeneSearch Assay results:None of the8DCIS patients showed a positive result. In12DCIS-MIs,2patients were positive. The results were fully consistent with the results of serial sectioning.
Conclusions:(1) Based on our currently available data, the routine use of SLNB in all patients with DCIS or DCIS-MI is not warranted. It is necessary to select certain kind of patients initially diagnosed with DCIS to undergo SLNB. However, it is also acknowledged that there are still no definite risk factors used to indicate an invasive component will be found after surgery.(2) Selected DCIS-MI patients with large tumor, high grade, several invasive clusters and vascular invasion seem to need a concomitant SLNB. Nevertheless, this should be certified by further investigation with larger numbers of patients and long follow-up.(3) Most of the SLN-positive DCIS or DCIS-MI patients were micrometastases or ITCs whose clinical significance and prognostic implications is still in controversy.
Part Ⅲ Expressions and significance of aB-crystallin and Galectin-7in breast cancer with different metastatic types of SLN
Objective:The purpose of the study is to use aB-crystallin and Galectin-7to detect the expression in breast cancers with different metastatic types of SLN, and to explore their significance.
Methods:One hundred and seventy four patients with IDC not otherwise specified who underwent SLNB between2005and March2009at FUSCC were enrolled in our cohort. The paraffin-embedded tissue samples of the primary breast cancer, the corresponding normal breast and the SLNs of macrometastatic cases were collected and included in tissue microarrays (TMAs), and stained with antibodies against aB-crystallin and Galectin-7.
Results:(1) All patients were female. The ages ranged from28to85years (mean51years, median51years). The tumor size ranged from0to5.5cm, with a mean of2.2cm. A total of484SLNs was successfully detected with an average of3SLNs per patient. Among these174patients,96cases were diagnosed as macrometastases,23cases were micrometastases, and the other55cases were free of metastasis (including5ITCs).(2) Expression of aB-crystallin:Fifty-nine out of the96(61.4%) macrometastatic cases were positive for aB-crystallin. Eight out of the23(34.8%) micrometastatic cases were positive for aB-crystallin. Twelve out of the55(21.8%) SLN-negative cases were positive for aB-crystallin. In the metastasis group (including macrometastasis and micrometastasis), the expression of aB-crystallin was significantly higher than the non-metastasis group{χ2=18.045, P=0.000). The expression of aB-crystallin in macrometastasis group was statistically higher than the non-metastasis group (χ2=22.056, P=0.000). The SLN-metastatic tumors showed a significantly increased aB-crystallin protein-positive rate than the primary tumors (86.8%vs61.4%, χ2=12.631, P=0.000). Our study also revealed that aB-crystallin protein levels were gradually and significantly elevated with the increase of histological grade (χ2=7.306, P=0.026).(3) Expression of Galectin-7:Although there was no obvious difference in the cytoplasmic Galectin-7expressions among the three different metastasis groups (χ2=2.398,P=0.301), a significantly different nuclear-positive rate can be observed. In the metastasis group (including macrometastasis and micrometastasis), the nuclear-positive rate of Galectin was significantly lower than the non-metastasis group (χ2=18.045, P=0.000). The nuclear expression of Galectin-7in macrometastasis group was statistically lower than the non-metastasis group (χ2=6.959, P=0.008). The SLN-metastatic tumors showed a significantly decreased Galectin-7nuclear-positive rate than the primary tumors (17.6%vs45.8%, χ2=14.063, P=0.000), while the SLN-metastatic tumors showed a significantly increased Galectin-7cytoplasm-positive rate than the primary tumors (strong positive cases:54.4%vs35.4%, χ2=9.433, P=0.007). The nuclear expression of Galectin-7levels were gradually and significantly decreased with the increase of histological grade (χ2=16.732, P=0.000). In HER2overexpressing and triple-negative groups, the nuclear-positive rate of Galectin-7is lower than luminal A or luminal B group.
Conclusions:The expression of aB-crystallin may play an active role in the metastasis of breast cancer, and might be served as an important parameter for determining tumor biological behavior. The early nuclear expression of Galectin-7may be a negative regulatory factor in breast cancer development, while the gradual disappearance of Galectin-7nuclear expression is likely to be a sign of breast cancer progression.
引文
[1]Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol,2005,23(30):7703-7720.
[2]Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer [J]. Oncologist,2004,9(6):606-616.
[3]Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases[J]. Cancer,1989,63(1):181-187.
[4]Warmuth MA, Bowen G, Prosnitz LR, et al. Complications of axillary lymph node dissection for carcinoma of the breast:a report based on a patient survey [J]. Cancer,1998,83(7):1362-1368.
[5]Kuehn T, Klauss W, Darsow M, et al. Long-term morbidity following axillary dissection in breast cancer patients--clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors [J]. Breast Cancer Res Treat,2000,64(3):275-286.
[6]Petrek JA, Senie RT, Peters M, et al. Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis[J]. Cancer,2001,92(6):1368-1377.
[7]Schrenk P, Rieger R, Shamiyeh A, et al. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma[J]. Cancer,2000,88:608-614.
[8]Silberman AW, McVay C, Cohen JS, et al. Comparative morbidity of axillary lymph node dissection and the sentinel lymph node technique:implications for patients with breast cancer[J]. Ann Surg,2004,240(1):1-6.
[9]Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial[J]. J Natl Cancer Inst,2006,98(9):599-609.
[10]Latosinsky S, Dabbs K, Moffat F. Canadian Association of General Surgeons and American College of Surgeons Evidence-Based Reviews in Surgery.27. Quality-of-life outcomes with sentinel node biopsy versus standard axillary treatment in patients with operable breast cancer. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial[J]. Can J Surg,2008,51(6):483-485.
[11]ASCO guideline recommendations for sentinel lymph node biopsy in early stage breast cancer[J]. J Clin Oncol,2005,23:7703-7720.
[12]Blumencranz P, Whitworth PW, Deck K, et al. Sentinel node staging for breast cancer:intraoperative molecular pathology overcomes conventional histologic sampling errors[J]. Am J Surg,2007,194:426-432.
[13]Julian TB, Blumencranz P, Deck K, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer [J]. J Clin Oncol,2008,26(20):3338-3345.
[14]Tamaki Y, Akiyama F, Iwase T, et al. Molecular detection of lymph node metastases in breast cancer patients:results of a multicenter trial using the one-step nucleic acid amplification assay [J]. Clin Cancer Res, 2009,15(8):2879-2884.
[15]Schem C, Maass N, Bauerschlag DO, et al. One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group[J]. Virchows Arch, 2009,454(2):203-210.
[16]Visser M, Jiwa M, Horstman A, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer[J]. Int J Cancer,2008,122(11):2562-2567.
[17]Sakr R, Antoine M, Barranger E, et al. Value of sentinel lymph node biopsy in breast ductal carcinoma in situ upstaged to invasive carcinoma.[J]. Breast J, 2008,14(1):55-60.
[18]Schwartz GF, Solin LJ, Olivotto IA, et al. The consensus conference on the treatment of in situ ductal carcinoma of the breast, April 22-25,1999[J]. Breast, 2000,9(4):177-186.
[19]Morrow M, Venta L, Stinson T, et al. Prospective comparison of stereotactic core biopsy and surgical excision as diagnostic procedures for breast cancer patients [J]. Ann Surg,2001,233(4):537-541.
[20]Klauber-DeMore N, Tan LK, Liberman L, et al. Sentinel lymph node biopsy:is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?[J]. Ann Surg Oncol,2000,7(9):636-642.
[21]Sakr R, Barranger E, Antoine M, et al. Ductal carcinoma in situ:value of sentinel lymph node biopsy[J]. J Surg Oncol,2006,94(5):426-430.
[22]D'Eredita G, Giardina C, Napoli A, et al. Sentinel lymph node biopsy in patients with pure and high-risk ductal carcinoma in situ of the breast.[J]. Tumori, 2009,95(6):706-711.
[23]Sener SF, Winchester DJ, Martz CH, et al. Lymphedema after sentinel lymphadenectomy for breast carcinoma[J]. Cancer,2001,92(4):748-752.
[24]Kuerer HM, Wayne JD, Ross MI. Anaphylaxis during breast cancer lymphatic mapping[J]. Surgery,2001,129(1):119-120.
[25]Aydogan F, Celik V, Uras C, et al. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2008,195(2):277-278.
[26]Saft S, Sarap M. Anaphylaxis during sentinel lymph node mapping[J]. JAAPA, 2007,20(9):26-28.
[27]Thevarajah S, Huston TL, Simmons RM. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2005,189(2):236-239.
[28]Chelouche-Lev D, Kluger HM, Berger AJ, et al. alphaB-crystallin as a marker of lymph node involvement in breast carcinoma[J]. Cancer, 2004,100(12):2543-2548.
[29]Saussez S, Kiss R. Galectin-7[J]. Cell Mol Life Sci,2006,63(6):686-697.
[30]Demers M, Rose AA, Grosset AA, et al. Overexpression of galectin-7, a myoepithelial cell marker, enhances spontaneous metastasis of breast cancer cells[J]. Am J Pathol,2010,176(6):3023-3031.
[1]Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol,2005,23(30):7703-7720.
[2]Motomura K, Nagumo S, Komoike Y, et al. Accuracy of imprint cytology for intraoperative diagnosis of sentinel node metastases in breast cancer [J]. Ann Surg, 2008,247(5):839-842.
[3]Tew K, Irwig L, Matthews A, et al. Meta-analysis of sentinel node imprint cytology in breast cancer[J]. Br J Surg,2005,92(9):1068-1080.
[4]Perez-Sanchez VM, Vela-Chavez TA, Villarreal-Colin P, et al. Intraoperative touch imprint cytology of sentinel lymph nodes in breast cancer:experience at a tertiary care center in Mexico[J]. Med Oncol,2010,27(2):233-236.
[5]Creager AJ, Geisinger KR, Shiver SA, et al. Intraoperative evaluation of sentinel lymph nodes for metastatic breast carcinoma by imprint cytology[J]. Mod Pathol, 2002,15(11):1140-1147.
[6]Cox C, Centeno B, Dickson D, et al. Accuracy of intraoperative imprint cytology for sentinel lymph node evaluation in the treatment of breast carcinoma[J]. Cancer,2005,105(1):13-20.
[7]Langer I, Guller U, Berclaz G, et al. Accuracy of frozen section of sentinel lymph nodes:a prospective analysis of 659 breast cancer patients of the Swiss multicenter study [J]. Breast Cancer Res Treat,2009,113(1):129-136.
[8]Creager AJ, Geisinger KR. Intraoperative Evaluation of Sentinel Lymph Nodes for Breast Carcinoma:Current Methodologies [J]. Adv Anat Pathol, 2002,9(4):233-243.
[9]Noriaki W, Shigeru I, Takahiro H, et al. Evaluation of Intraoperative Frozen Section Diagnosis of Sentinel Lymph Nodes in Breast Cancer[J]. Jpn J Clin Oncol,2004,34(3):1113-17.
[10]van de Vrande S, Meijer J, Rijnders A, et al. The value of intraoperative frozen section examination of sentinel lymph nodes in breast cancer [J]. Eur J Surg Oncol, 2009,35(3):276-280.
[11]Chao C. The use of frozen section and immunohistchemistry for sentinel lymph node biopsy in breast cancer[J]. Am Surg,2004,70(5):414-419.
[12]Bernstein JL, Godbold JH, Raptis G, et al. Identification of mammaglobin as a novel serum marker for breast cancer [J]. Clin Cancer Res, 2005,11(18):6528-6535.
[13]Zehentner BK, Carter D. Mammaglobin:a candidate diagnostic marker for breast cancer[J]. Clin Biochem,2004,37(4):249-257.
[14]Schoenfeld A, Kruger KH, Gomm J, et al. The detection of micrometastases in the peripheral blood and bone marrow of patients with breast cancer using immunohistochemistry and reverse transcriptase polymerase chain reaction for keratin 19[J]. Eur J Cancer,1997,33(6):854-861.
[15]Backus J, Laughlin T, Wang Y, et al. Identification and characterization of optimal gene expression markers for detection of breast cancer metastasis[J]. J Mol Diagn,2005,7(3):327-336.
[16]Julian TB, Blumencranz P, Deck K, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer [J]. J Clin Oncol,2008,26(20):3338-3345.
[17]Tamaki Y, Akiyama F, Iwase T, et al. Molecular detection of lymph node metastases in breast cancer patients:results of a multicenter trial using the one-step nucleic acid amplification assay [J]. Clin Cancer Res, 2009,15(8):2879-2884.
[18]Schem C, Maass N, Bauerschlag DO, et al. One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group[J]. Virchows Arch, 2009,454(2):203-210.
[19]Visser M, Jiwa M, Horstman A, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer[J]. Int J Cancer,2008,122(11):2562-2567.
[20]Cserni G, Bianchi S, Vezzosi V, et al. Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions [J]. Eur J Cancer, 2008,44(15):2185-2191.
[21]Osako T, Iwase T, Kimura K, et al. Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer:A comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology [J]. Cancer,2011.
[22]Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol,2005,23(30):7703-7720.
[23]Reed J, Rosman M, Verbanac KM, et al. Prognostic Implications of Isolated Tumor Cells and Micrometastases in Sentinel Nodes of Patients with Invasive Breast Cancer:10-Year Analysis of Patients Enrolled in the Prospective East Carolina University/Anne Arundel Medical Center Sentinel Node Multicenter Study[J]. J Am Coll Surg,2009,208(3):334-340.
[24]Cox CE, Kiluk JV, Riker AL. Significance of sentinel node micrometastases in human breast cancer[J]. J Am Coll Surg,2008,206:261-268.
[25]Marinho VF, Zagury MS, Caldeira LG, et al. Relationship between histologic features of primary breast carcinomas and axillary lymph node micrometastases: Detection and prognostic significance [J]. Appl Immunohistochem Mol Morphol, 2006,14(4):426-431.
[26]Bulte CS, van der Heiden-van der Loo M, Hennipman A. Axillary recurrence rate after tumour negative and micrometastatic positive sentinel node procedures in breast cancer patients, a population based multicenter study [J]. Eur J Surg Oncol, 2009,35(1):25-31.
[27]Hansen NM, Grube B, Ye X, et al. Impact of micrometastases in the sentinel node of patients with invasive breast cancer[J]. J Clin Oncol,2009,27(28):4679-4684.
[28]Onishi T, Jinno H, Takahashi M, et al. Non-sentinel lymph node status and prognosis of breast cancer patients with micrometastatic sentinel lymph nodes[J]. Eur Surg Res,2010,45(3-4):344-349.
[29]Langer I, Marti WR, Guller U, et al. Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy [J]. Ann Surg, 2005,241(1):152-158.
[30]Wasif N, Ye X, Giuliano A E. Survey of ASCO members on management of sentinel node micrometastases in breast cancer:variation in treatment recommendations according to specialty [J]. Ann Surg Oncol, 2009,16(9):2442-2449.
[31]Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases:the American College of Surgeons Oncology Group Z0011 randomized trial[J]. Ann Surg,2010,252(3):426-432,432-433.
[32]Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis:a randomized clinical trial[J]. JAMA,2011,305(6):569-575.
[33]Cserni G. Axillary staging of breast cancer and the sentinel node[J]. J Clin Pathol, 2000,53(10):733-741.
[34]Turner RR, Ollila DW, Stern S, et al. Optimal histopathologic examination of the sentinel lymph node for breast carcinoma staging[J]. Am J Surg Pathol, 1999,23(3):263-267.
[35]Cserni G, Amendoeira I, Apostolikas N, et al. Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology[J]. J Clin Pathol,2004,57(7):695-701.
[36]Blumencranz P, Whitworth PW, Deck K, et al. Sentinel node staging for breast cancer:intraoperative molecular pathology overcomes conventional histologic sampling errors[J]. Am J Surg,2007,194:426-432.
[37]Julian TB, Blumencranz P, Deck K, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer.[J]. J Clin Oncol,2008,26(20):3338-3345.
[38]Martin Martinez MD, Veys I, Majjaj S, et al. Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes[J]. Eur J Surg Oncol,2009,35(4):387-392.
[39]Viale G, Dell'Orto P, Biasi MO, et al. comparative evaluation of an Extensive Histopathologic Examination and a Real-Time Reverse-Transcription-Polymerase chain Reaction Assay for Mammaglobin and Cytokeratin 19 on Axillary Sentinel Lymph Nodes of Breast Carcinoma Patients[J]. Ann Surg,2008,247(1):136-142.
[40]Lefferts JA, Bartels CL, Tsongalis GJ. Molecular oncology:current trends in diagnostics [J]. Future Oncol,2008,4(1):61-70.
[41]Veys I, Durbecq V, Majjaj S, et al. Eighteen months clinical experience with the GeneSearch breast lymph node assay [J]. Am J Surg,2009,198(2):203-209.
[42]Chen JJ, Yang BL, Zhang JX, et al. The evaluation and optimization of intraoperative touch imprint cytology for sentinel lymph nodes in early-stage breast cancer in China[J]. World J Surg,2010,34(10):2325-2332.
[43]Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging manual (7th ed)[M]. New York:Springer,2010.
[44]Guillanders WE, Mikhitarian K, Hebert R, et al. Molecular detection of micrometastatic breast cancer in histopathologynegative axillary lymph nodes correlates with traditional predictors of prognosis[J]. Ann Surg, 2004,239:828-840.
[45]Liberman L. Pathologic analysis of sentinel lymph nodes in breast carcinoma[J]. Cancer,2000,88:971-977.
[46]Ouellette J, Richard D, Maicas E. Correction of RT-PCR for mammaglobin genes,MGB1 and MGB2, identifies breast cancer micrometastases in sentinel lymph nodes[J]. Am J Clin Pathol,2004,122:813.
[47]Valeria D, Daniela A, Fernando P, et al. Sentinel Lymph Node Molecular Pathology in Breast Carcinoma[J]. Diagn Mol Pathol,2008,17:214-219.
[48]Ouellette RJ, Richard D, Maicas E. RT-PCR for mammaglobin genes, MGB1 and MGB2, identifies breast cancer micrometastases in sentinel lymph nodes [J]. Am J Clin Pathol,2004,121:637-643.
[49]Zehentner B, Persing D, Deme A, et al. Mammaglobin as a novel breast cancer biomarker:multigene reverse transcription PCR assay and sandwich ELISA[J]. Clin Chem,2004,50:2069-2076.
[50]Tsujimoto M, Nakabayashi K, Yoshidome K, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients [J]. Clin Cancer Res,2007,13(16):4807-4816.
[51]Le Frere-Belda MA, Bats AS, Gillaizeau F, et al. Diagnostic performance of one-step nucleic acid amplification for intraoperative sentinel node metastasis detection in breast cancer patients[J]. Int J Cancer,2012,130(10):2377-2386.
[52]Snook KL, Layer GT, Jackson PA, et al. Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma[J]. Br J Surg, 2011,98(4):527-535.
[53]Feldman S, Krishnamurthy S, Gillanders W, et al. A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes[J]. Cancer,2011,117(12):2599-2607.
[54]Bernet L, Cano R, Martinez M, et al. Diagnosis of the sentinel lymph node in breast cancer:a reproducible molecular method:a multicentric Spanish study[J]. Histopathology,2011,58(6):863-869.
[55]Turner RR, Ollila DW, Stem S, et al. Optimal histopathologic examination of the sentinel lymph node for breast carcinoma staging[J]. Am J Surg Pathol, 1999,23(3):263.
[56]Nahrig J, Richter T, Kowolik J, et al. Comparison of different histopathological methods for the examination of sentinel lymph nodes in breast cancer [J]. Anticancer Res,2000,20(3B):2209-2212.
[57]Viale G, Maiorano E, Mazzarol G, et al. Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma[J]. Cancer,2001,92(6):1378-1384.
[58]Kanngurn S, Chewatanakornkul S, Premprapha T, et al. Comparability of different pathologic protocols in sentinel lymph node evaluation:an analysis of two step-sectioning methods for the same patients with breast cancer[J]. Arch Pathol Lab Med.,2009,133(9):1437-1440.
[59]van Diest PJ, Peterse HL, Borgstein PJ, et al. Pathological investigation of sentinel lymph nodes[J]. Eur J Nucl Med,1999,26(Suppl):S43-S49.
[60]Schwartz GF, Giuliano AE, Veronesi U. Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast April 19 to 22,2001, Philadelphia, Pennsylvania[J]. Hum Pathol,2002,33(6):579-589.
[61]Cserni G, Amendoeira I, Apostolikas N, et al. Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines[J]. Eur J Cancer,2003,39(12):1654-1667.
[62]Turner RR, Donald LW, Gabor C, et al. Nodal Stage Classification for Breast Carcinoma:Improving Interobserver Reproducibility Through Standardized Histologic Criteria and Image-Based Training[J]. J Clin Oncol,2008,26:258-265.
[63]Cserin G, Sapino A, Decker T. Discriminating between micrometastases and isolated tumor cells in a regional and institutional setting[J].The Breast, 2006,15:347-354.
[64]Rutgers EJ. Sentinel Node Biopsy:Interpretation and Management of Patients With Immunohistochemistry-Positive Sentinel Nodes and Those With Micrometastases [J]. J Clin Oncol,2008,26(5):698-702.
[65]Ludwig breast cancer study group. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. International (Ludwig) Breast Cancer Study Group[J]. Lancet,1990,335(8705):1565-1568.
[66]Houvenaeghel G, Nos C, Mignotte H. Micrometastases in sentinel lymph node in a multicentric study:redictive factors of nonsentinel lymph node involvement [J]. J Clin Oncol,2006,24(12):1814-1822.
[67]Viale G, Maiorano E, Pruneri G. Predicting the risk for additional axillary metastases in patients with breast carcinoma and positive sentinel lymph node biopsy[J]. Ann Surg,2005,241(2):319-325.
[1]Schwartz GF, Solin LJ, Olivotto IA, et al. The consensus conference on the treatment of in situ ductal carcinoma of the breast, April 22-25,1999[J]. Breast, 2000,9(4):177-186.
[2]Cox CE, Nguyen K, Gray RJ, et al. Importance of lymphatic mapping in ductal carcinoma in situ (DCIS):why map DCIS?[J]. Am Surg,2001,67(6):513-519, 519-521.
[3]Cserni G. Sentinel lymph node biopsy as a tool for the staging of ductal carcinoma in situ in patients with breast carcinoma[J]. Surg Today, 2002,32(2):99-103.
[4]Dominguez FJ, Golshan M, Black DM, et al. Sentinel node biopsy is important in mastectomy for ductal carcinoma in situ[J]. Ann Surg Oncol, 2008,15(1):268-273.
[5]Farkas EA, Stolier AJ, Teng SC, et al. An argument against routine sentinel node mapping for DCIS[J]. Am Surg,2004,70:13-17.
[6]Intra M, Veronesi P, Mazzarol G, et al. Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast[J]. Arch Surg, 2003,138(3):309-313.
[7]Katz A, Gage I, Evans S, et al. Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer[J]. Am J Surg, 2006,191(6):761-766.
[8]Kelly TA, Kim JA, Patrick R, et al. Axillary lymph node metastases in patients with a final diagnosis of ductal carcinoma in situ[J]. Am J Surg, 2003,186(4):368-370.
[9]Mabry H, Giuliano AE, Silverstein MJ. What is the value of axillary dissection or sentinel node biopsy in patients with ductal carcinoma in situ?[J]. Am J Surg, 2006,192(4):455-457.
[10]Sakr R, Antoine M, Barranger E, et al. Value of sentinel lymph node biopsy in breast ductal carcinoma in situ upstaged to invasive carcinoma[J]. Breast J, 2008,14(1):55-60.
[11]Veronesi P, Intra M, Vento AR, et al. Sentinel lymph node biopsy for localised ductal carcinoma in situ?[J]. Breast,2005,14(6):520-522.
[12]Zavagno G, Carcoforo P, Marconato R, et al. Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast[J]. BMC Cancer,2005,5:28.
[13]Sakr R, Barranger E, Antoine M, et al. Ductal carcinoma in situ:value of sentinel lymph node biopsy[J]. J Surg Oncol,2006,94(5):426-430.
[14]van la Parra RF, Ernst MF, Barneveld PC, et al. The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast[J]. Eur J Surg Oncol,2008,34(6):631-635.
[15]Klauber-DeMore N, Tan LK, Liberman L, et al. Sentinel lymph node biopsy:is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?[J]. Ann Surg Oncol,2000,7(9):636-642.
[16]D'Eredita G, Giardina C, Napoli A, et al. Sentinel lymph node biopsy in patients with pure and high-risk ductal carcinoma in situ of the breast.[J]. Tumori, 2009,95(6):706-711.
[17]van Rijk M C, Peterse J L, Nieweg O E, et al. Additional axillary metastases and stage migration in breast cancer patients with micrometastases or submi-crometastases in sentinel lymph nodes[J]. Cancer,2006,107:467-471.
[18]Cserni G, Bianchi S, Vezzosi V, et al. Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions[J]. Eur J Cancer, 2008,44(15):2185-2191.
[19]American Joint Committee On Cancer. AJCC cancer staging manual [M],7 th ed. New York:Springer,2010:354.
[20]Fentiman IS.8. The dilemma of in situ carcinoma of the breast[J]. Int J Clin Pract, 2001,55(10):680-683.
[21]Ernster VL, Ballard-Barbash R, Barlow WE, et al. Detection of ductal carcinoma in situ in women undergoing screening mammography[J]. J Natl Cancer Inst, 2002,94(20):1546-1554.
[22]Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases[J]. Cancer,1989,63(1):181-187.
[23]Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer[J]. Oncologist,2004,9(6):606-616.
[24]Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol,2005,23(30):7703-7720.
[25]Warmuth MA, Bowen G, Prosnitz LR, et al. Complications of axillary lymph node dissection for carcinoma of the breast:a report based on a patient survey[J]. Cancer,1998,83(7):1362-1368.
[26]Kuehn T, Klauss W, Darsow M, et al. Long-term morbidity following axillary dissection in breast cancer patients--clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors [J]. Breast Cancer Res Treat,2000,64(3):275-286.
[27]Petrek JA, Senie RT, Peters M, et al. Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis[J]. Cancer,2001,92(6):1368-1377.
[28]National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology-Breast Cancer Guideline 2011.
[29]Goyal A, Douglas-Jones A, Monypenny I, et al. Is there a role of sentinel lymph node biopsy in ductal carcinoma in situ?:analysis of 587 cases [J]. Breast Cancer Res Treat,2006,98(3):311-314.
[30]Ansari B, Ogston SA, Purdie CA, et al. Meta-analysis of sentinel node biopsy in ductal carcinoma in situ of the breast [J]. Br J Surg,2008,95(5):547-554.
[31]Pendas S, Dauway E, Giuliano R, et al. Sentinel node biopsy in ductal carcinoma in situ patients[J]. Ann Surg Oncol,2000,7(1):15-20.
[32]Schrenk P, Rieger R, Shamiyeh A, et al. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma[J]. Cancer,2000,88(3):608-614.
[33]Sener SF, Winchester DJ, Martz CH, et al. Lymphedema after sentinel lymphadenectomy for breast carcinoma[J]. Cancer,2001,92(4):748-752.
[34]Kuerer HM, Wayne JD, Ross MI. Anaphylaxis during breast cancer lymphatic mapping[J]. Surgery,2001,129(1):119-120.
[35]Aydogan F, Celik V, Uras C, et al. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2008,195(2):277-278.
[36]Saft S, Sarap M. Anaphylaxis during sentinel lymph node mapping[J]. JAAPA, 2007,20(9):26-28.
[37]Thevarajah S, Huston TL, Simmons RM. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2005,189(2):236-239.
[38]Yen TW, Hunt KK, Ross MI, et al. Predictors of invasive breast cancer in patients with an initial diagnosis of ductal carcinoma in situ:a guide to selective use of sentinel lymph node biopsy in management of ductal carcinoma in situ[J]. J Am Coll Surg,2005,200(4):516-526.
[39]Intra M, Brito J A D, Soteldo J, et al. Sentinel Lymph Node Biopsy in Intraductal Carcinoma of the Breast with Microinvasion[J]. Intl J Cancer Res,2005,1(1):1-4.
[40]Intra M, Zurrida S, Maffini F, et al. Sentinel lymph node metastasis in microinvasive breast cancer[J]. Ann Surg Oncol,2003,10(10):1160-1165.
[41]Moran CJ, Kell MR, Flanagan FL, et al. Role of sentinel lymph node biopsy in high-risk ductal carcinoma in situ patients[J]. Am J Surg,2007,194(2):172-175.
[42]Moran CJ, Kell MR, Kerin MJ. The role of sentinel lymph node biopsy in ductal carcinoma in situ[J]. Eur J Surg Oncol,2005,31 (10):1105-1111.
[43]Moore KH, Sweeney KJ, Wilson ME, et al. Outcomes for women with ductal carcinoma-in-situ and a positive sentinel node:a multi-institutional audit[J]. Ann Surg Oncol,2007,14(10):2911-2917.
[44]Huo L, Sneige N, Hunt KK, et al. Predictors of invasion in patients with core-needle biopsy-diagnosed ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy in ductal carcinoma in situ[J]. Cancer,2006,107(8):1760-1768.
[45]King TA, Farr GJ, Cederbom GJ, et al. A mass on breast imaging predicts coexisting invasive carcinoma in patients with a core biopsy diagnosis of ductal carcinoma in situ[J]. Am Surg,2001,67(9):907-912.
[46]Renshaw AA. Predicting invasion in the excision specimen from breast core needle biopsy specimens with only ductal carcinoma in situ[J]. Arch Pathol Lab Med,2002,126(1):39-41.
[47]Silver SA, Tavassoli FA. Mammary ductal carcinoma in situ with microinvasion[J]. Cancer,1998,82(12):2382-2390.
[48]Pimiento JM, Lee MC, Esposito NN, et al. Role of axillary staging in women diagnosed with ductal carcinoma in situ with microinvasion[J].J Oncol Pract, 2011,7(5):309-313.
[49]Adamovich TL, Simmons RM. Ductal carcinoma in situ with microinvasion[J]. Am J Surg,2003,186(2):112-116.
[50]Silverstein MJ, Lagios MD. Ductal carcinoma in situ with microinvasion[M]//MJ S. Ductal Carcinoma in Situ of the Breast. Philadelphia:Lippincott Williams and Wilkins,2002:557-562.
[51]de Mascarel I, MacGrogan G, Mathoulin-Pelissier S, et al. Breast ductal carcinoma in situ with microinvasion:a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas[J]. Cancer,2002,94(8):2134-2142.
[52]Prasad ML, Osborne MP, Giri DD, et al. Microinvasive carcinoma (Tlmic) of the breast:clinicopathologic profile of 21 cases[J]. Am J Surg Pathol, 2000,24(3):422-428.
[53]Yang M, Moriya T, Oguma M, et al. Microinvasive ductal carcinoma (Tlmic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases[J]. Pathol Int,2003,53(7):422-428.
[54]Vieira CC, Mercado CL, Cangiarella JF, et al. Microinvasive ductal carcinoma in situ:clinical presentation, imaging features, pathologic findings, and outcome[J]. Eur J Radiol,2010,73(1):102-107.
[55]Zavagno G, Belardinelli V, Marconato R, et al. Sentinel lymph node metastasis from mammary ductal carcinoma in situ with microinvasion[J]. Breast, 2007,16(2):146-151.
[56]Ko BS, Lim WS, Kim HJ, et al. Risk factor for axillary lymph node metastases in microinvasive breast cancer[J]. Ann Surg Oncol,2012,19(1):212-216.
[57]Parikh RR, Haffty BG, Lannin D, et al. Ductal Carcinoma In Situ with Microinvasion:Prognostic Implications, Long-Term Outcomes, and Role of Axillary Evaluation[J]. Int J Radiat Oncol Biol Phys,2010.
[58]Wong JH, Kopald KH, Morton DL. The impact of microinvasion on axillary node metastases and survival in patients with intraductal breast cancer[J]. Arch Surg, 1990,125(10):1298-1301,1301-1302.
[59]Solin LJ, Fowble BL, Yeh IT, et al. Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation[J]. Int J Radiat Oncol Biol Phys,1992,23(5):961-968.
[60]Rosner D, Lane WW, Penetrante R. Ductal carcinoma in situ with microinvasion. A curable entity using surgery alone without need for adjuvant therapy [J]. Cancer, 1991,67(6):1498-1503.
[61]Lara JF, Young SM, Velilla RE, et al. The relevance of occult axillary micrometastasis in ductal carcinoma in situ:a clinicopathologic study with long-term follow-up[J]. Cancer,2003,98(10):2105-2113.
[62]Murphy CD, Jones JL, Javid SH, et al. Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion?[J]. Am J Surg,2008,196(4):566-568.
[1]Wolmark N, Fisher B. Surgery in the primary treatment of breast cancer[J]. Breast Cancer Res Treat,1981,1 (4):339-348.
[2]Schrenk P, Rieger R, Shamiyeh A, et al. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma[J]. Cancer,2000,88:608-614.
[3]Husted Madsen A, Haugaard K, Soerensen J, et al. Arm morbidity following sentinel lymph node biopsy or axillary lymph node dissection:a study from the Danish Breast Cancer Cooperative Group [J]. Breast,2008,17(2):138-147
[4]Sener SF, Winchester DJ, Martz CH, et al. Lymphedema after sentinel lymphadenectomy for breast carcinoma[J]. Cancer,2001,92(4):748-752.
[5]Kuerer HM, Wayne JD, Ross MI. Anaphylaxis during breast cancer lymphatic mapping[J]. Surgery,2001,129(1):119-120.
[6]Aydogan F, Celik V, Uras C, et al. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2008,195(2):277-278.
[7]Saft S, Sarap M. Anaphylaxis during sentinel lymph node mapping[J]. JAAPA, 2007,20(9):26-28.
[8]Thevarajah S, Huston TL, Simmons RM. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2005,189(2):236-239.
[9]Bevilacqua JL, Kattan MW, Fey JV, et al. Doctor, what are my chances of having a positive sentinel node? A validated nomogram for risk estimation [J]. J Clin Oncol,2007,25(24):3670-3679.
[10]Chelouche-Lev D, Kluger HM, Berger AJ, et al. alphaB-crystallin as a marker of lymph node involvement in breast carcinoma. [J]. Cancer, 2004,100(12):2543-2548.
[11]Saussez S, Kiss R. Galectin-7[J]. Cell Mol Life Sci,2006,63(6):686-697.
[12]Demers M, Rose AA, Grosset AA, et al. Overexpression of galectin-7, a myoepithelial cell marker, enhances spontaneous metastasis of breast cancer cells[J]. Am J Pathol,2010,176(6):3023-3031.
[13]Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer:experience from a large study with long-term follow-up [J]. Histopathology,1991,19(5):403-410.
[14]Hutterer M, Knyazev P, Abate A, et al. Axl and growth arrest-specific gene 6 are frequently overexpressed in human gliomas and predict poor prognosis in patients with glioblastoma multiforme[J]. Clin Cancer Res,2008,14(1):130-138.
[15]Reschke M, Mihic-Probst D, van der Horst EH, et al. HER3 is a determinant for poor prognosis in melanoma[J]. Clin Cancer Res,2008,14(16):5188-5197.
[16]Remmele W, Schicketanz KH. Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS)[J]. Pathol Res Pract, 1993,189(8):862-866.
[17]DeSantis C, Siegel R, Bandi P, et al. Breast cancer statistics,2011[J]. CA Cancer J Clin,2011,61(6):409-418.
[18]van de Vijver MJ, He YD, Van'T VL, et al. A gene-expression signature as a predictor of survival in breast cancer[J]. N Engl J Med,2002,347(25):1999-2009.
[19]Dubin RA, Ally AH, Chung S, et al. Human alpha B-crystallin gene and preferential promoter function in lens[J]. Genomics,1990,7(4):594-601.
[20]Clark JI, Muchowski PJ. Small heat-shock proteins and their potential role in human disease[J]. Curr Opin Struct Biol,2000,10(1):52-59.
[21]Kamradt MC, Lu M, Werner ME, et al. The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3[J]. J Biol Chem,2005,280(12):11059-11066.
[22]Kamradt MC, Chen F, Sam S, et al. The small heat shock protein alpha B-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation[J]. J Biol Chem,2002,277(41):38731-38736.
[23]Kamradt MC, Chen F, Cryns VL. The small heat shock protein alpha B-crystallin negatively regulates cytochrome c-and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation[J]. J Biol Chem, 2001,276(19):16059-16063.
[24]Mao YW, Liu JP, Xiang H, et al. Human alphaA-and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis[J]. Cell Death Differ,2004,11 (5):512-526.
[25]Watanabe G, Kato S, Nakata H, et al. alphaB-crystallin:a novel p53-target gene required for p53-dependent apoptosis[J]. Cancer Sci,2009,100(12):2368-2375.
[26]Kase S, He S, Sonoda S, et al. alphaB-crystallin regulation of angiogenesis by modulation of VEGF.[J]. Blood,2010,115(16):3398-3406.
[27]Morrison LE, Whittaker RJ, Klepper RE, et al. Roles for alphaB-crystallin and HSPB2 in protecting the myocardium from ischemia-reperfusion-induced damage in a KO mouse model [J]. Am J Physiol Heart Circ Physiol, 2004,286(3):H847-H855.
[28]Vicart P, Caron A, Guicheney P, et al. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy[J]. Nat Genet,1998,20(1):92-95.
[29]Dabir DV, Trojanowski JQ, Richter-Landsberg C, et al. Expression of the small heat-shock protein alphaB-crystallin in tauopathies with glial pathology [J]. Am J Pathol,2004,164(1):155-166.
[30]Rekas A, Adda CG, Andrew AJ, et al. Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein:effects on amyloid fibril formation and chaperone activity [J]. J Mol Biol,2004,340(5):1167-1183.
[31]Raju I, Oonthonpan L, Abraham EC. Mutations in Human alphaA-Crystallin/sHSP Affect Subunit Exchange Interaction with alphaB-Crystallin[J]. PLoS One,2012,7(2):e31421.
[32]房爱菊,孟斌,刘文君，等a-B crystallin在乳腺浸润性导管癌中的表达及意义[J].山东大学学报(医学版),2008,46(3)：280-283.
[33]Moyano JV, Evans JR, Chen F, et al. AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer.[J]. J Clin Invest, 2006,116(1):261-270.
[34]Fan C, Oh DS, Wessels L, et al. Concordance among gene-expression-based predictors for breast cancer [J]. N Engl J Med,2006,355(6):560-569.
[35]Sitterding SM, Wiseman WR, Schiller CL, et al. AlphaB-crystallin:a novel marker of invasive basal-like and metaplastic breast carcinomas.[J]. Ann Diagn Pathol,2008,12(1):33-40.
[36]Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets[J]. Proc Natl Acad Sci U S A, 2003,100(14):8418-8423.
[37]Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications[J]. Proc Natl Acad Sci U S A,2001,98(19):10869-10874.
[38]Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours[J]. Nature,2000,406(6797):747-752.
[39]Livasy CA, Karaca G, Nanda R, et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma[J]. Mod Pathol,2006,19(2):264-271.
[40]Aoyama A, Steiger RH, Frohli E, et al. Expression of alpha B-crystallin in human brain tumors[J]. Int J Cancer,1993,55(5):760-764.
[41]Pinder SE, Balsitis M, Ellis 10, et al. The expression of alpha B-crystallin in epithelial tumours:a useful tumour marker?[J]. J Pathol,1994,174(3):209-215.
[42]Chin D, Boyle GM, Williams RM, et al. Alpha B-crystallin, a new independent marker for poor prognosis in head and neck cancer[J]. Laryngoscope, 2005,115(7):1239-1242.
[43]Bau DT, Tsai CW, Lin CC, et al. Association of alpha B-crystallin genotypes with oral cancer susceptibility, survival, and recurrence in Taiwan[J]. PLoS One, 2011,6(9):e16374.
[44]Magnaldo T, Bernerd F, Darmon M. Galectin-7, a human 14-kDa S-lectin, specifically expressed in keratinocytes and sensitive to retinoic acid[J]. Dev Biol,1995,168(2):259-271.
[45]Timmons PM, Colnot C, Cail I, et al. Expression of galectin-7 during epithelial development coincides with the onset of stratification [J]. Int J Dev Biol, 1999,43(3):229-235.
[46]Kuwabara I, Kuwabara Y, Yang RY, et al. Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release[J]. J Biol Chem,2002,277(5):3487-3497.
[47]Bernerd F, Sarasin A, Magnaldo T. Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes[J]. Proc Natl Acad Sci USA,1999,96(20):11329-11334.
[48]Ueda S, Kuwabara I, Liu FT. Suppression of tumor growth by galectin-7 gene transfer[J]. Cancer Res,2004,64(16):5672-5676.
[49]Kopitz J, Andre S, von Reitzenstein C, et al. Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells[J]. Oncogene,2003,22(40):6277-6288.
[50]Lu J, Pei H, Kaeck M, et al. Gene expression changes associated with chemically induced rat mammary carcinogenesis[J]. Mol Carcinog,1997,20(2):204-215.
[51]Rorive S, Eddafali B, Fernandez S, et al. Changes in galectin-7 and cytokeratin-19 expression during the progression of malignancy in thyroid tumors: diagnostic and biological implications[J]. Mod Pathol,2002,15(12):1294-1301.
[52]Chen J, He QY, Yuen AP, et al. Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis[J]. Proteomics, 2004,4(8):2465-2475.
[53]Zhu X, Ding M, Yu ML, et al. Identification of galectin-7 as a potential biomarker for esophageal squamous cell carcinoma by proteomic analysis[J]. BMC Cancer,2010,10:290.
[54]Lee JS, Lee Y, Jeon B, et al. EC-SOD induces apoptosis through COX-2 and galectin-7 in the epidermis[J]. J Dermatol Sci,2012,65(2):126-133.
[55]Saussez S, Decaestecker C, Lorfevre F, et al. Increased expression and altered intracellular distribution of adhesion/growth-regulatory lectins galectins-1 and -7 during tumour progression in hypopharyngeal and laryngeal squamous cell carcinomas [J]. Histopathology,2008,52(4):483-493.
[56]Demers M, Magnaldo T, St-Pierre Y. A novel function for galectin-7:promoting tumorigenesis by up-regulating MMP-9 gene expression[J]. Cancer Res, 2005,65(12):5205-5210.
[1]Lacroix M. Significance, detection and markers of disseminated breast cancer cells[J]. Endocr Relat Cancer,2006,13:1033-1067.
[2]Schrenk P, Rieger R, Shamiyeh A, et al. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast caicinoma[J]. Cancer,2000,88:608-614.
[3]Cabanas RM. Anatomy and biopsy of sentinel lymph nodes[J]. Urol Clin North Am,1992,19(2):267-276.
[4]Turner RR, Donald LW, Gabor C, et al. Nodal Stage Classification for Breast Carcinoma:Improving Interobserver Reproducibility Through Standardized Histologic Criteria and Image-Based Training[J]. J Clin Oncol,2008,26:258-265.
[5]Cserin G, Sapino A, Decker T. Discriminating between micrometastases and isolated tumor cells in a regional and institutional setting[J]. The Breast, 2006,15:347-354.
[6]Cserni G, Bianchi S, Vezzosi V, et al. Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions[J]. Eur J Cancer, 2008,44(15):2185-2191.
[7]Motomura K, Nagumo S, Komoike Y, et al. Accuracy of imprint cytology for intraoperative diagnosis of sentinel node metastases in breast cancer[J]. Ann Surg, 2008,247(5):839-842.
[8]Tew K, Irwig L, Matthews A, et al. Meta-analysis of sentinel node imprint cytology in breast cancer[J]. Br J Surg,2005,92(9):1068-1080.
[9]Chicken DW, Kocjan G, Falzon M, et al. Intraoperative touch imprint cytology for the diagnosis of sentinel lymph node metastases in breast cancer[J]. Br J Surg, 2006,93(5):572-576.
[10]Perez-Sanchez VM, Vela-Chavez TA, Villarreal-Colin P, et al. Intraoperative touch imprint cytology of sentinel lymph nodes in breast cancer:experience at a tertiary care center in Mexico[J]. Med Oncol.2010,27(2):233-236.
[11]Hamidian JA, Narayanan S, MacNeill F, et al. Testing the feasibility of intra-operative sentinel lymph node touch imprint cytology.[J]. Ann R Coll Surg Engl,2009,91(4):336-339.
[12]Contractor K, Gohel M, Al-Salami E, et al. Intra-operative imprint cytology for assessing the sentinel node in breast cancer:results of its routine use over 8 years.[J]. Eur J Surg Oncol,2009,35(1):16-20.
[13]Feng J, Bernacki EG. Intraoperative cytologic evaluation of sentinel lymph nodes in patients with breast carcinoma by scrape preparation[J]. Diagn Cytopathol, 2008,36(11):790-793.
[14]Creager AJ, Geisinger KR, Shiver SA, et al. Intraoperative evaluation of sentinel lymph nodes for metastatic breast carcinoma by imprint cytology [J]. Mod Pathol, 2002,15(11):1140-1147.
[15]Cox C, Centeno B, Dickson D, et al. Accuracy of intraoperative imprint cytology for sentinel lymph node evaluation in the treatment of breast carcinoma[J]. Cancer,2005,105(1):13-20.
[16]Motomura K, Nagumo S, Komoike Y, et al. Intraoperative imprint cytology for the diagnosis of sentinel node metastases in breast cancer[J]. Breast Cancer, 2007,14(4):350-353.
[17]Langer I, Guller U, Berclaz G, et al. Accuracy of frozen section of sentinel lymph nodes:a prospective analysis of 659 breast cancer patients of the Swiss multicenter study [J]. Breast Cancer Res Treat,2009,113(1):129-136.
[18]Creager AJ, Geisinger KR. Intraoperative Evaluation of Sentinel Lymph Nodes for Breast Carcinoma:Current Methodologies[J]. Adv Anat Pathol, 2002,9(4):233-243.
[19]Noriaki W, Shigeru I, Takahiro H, et al. Evaluation of Intraoperative Frozen Section Diagnosis of Sentinel Lymph Nodes in Breast Cancer[J]. Jpn J Clin Oncol,2004,34(3):113-117.
[20]van de Vrande S, Meijer J, Rijnders A, et al. The value of intraoperative frozen section examination of sentinel lymph nodes in breast cancer[J]. Eur J Surg Oncol, 2009,35(3):276-280.
[21]Chao C. The use of frozen section and immunohistchemistry for sentinel lymph node biopsy in breast cancer [J]. Am Surg,2004,70(5):414-419.
[22]Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol,2005,23(30):7703-7720.
[23]Cserni G, Amendoeira I, Apostolikas N, et al. Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology [J]. J Clin Pathol,2004,57(7):695-701.
[24]Goyal A, Mansel RE. Recent advances in sentinel lymph node biopsy for breast cancer.[J]. Curr Opin Oncol,2008,20(6):621-626.
[25]Giobuin SM, Kavanagh DO, Myers E, et al. The significance of immunohistochemistry positivity in sentinel nodes which are negative on haematoxylin and eosin in breast cancer [J]. Eur J Surg Oncol, 2009,35(12):1257-1260.
[26]Cserni G, Bianchi S, Vezzosi V. The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma[J]. J Clin Pathol.,2006,59(5):518-522.
[27]Cserni G, Gregori D, Merletti F, et al. Meta-analysis of non-sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer [J]. British Journal of Surgery,2004,91:1245-1252.
[28]Mullenix PS, Brown TA, Meyers MO, et al. The association of cytokeratin-only-positive sentinel lymph nodes and subsequent metastases in breast cancer [J]. Am J Surg,2005,189(5):606-609.
[29]Young JC, Hae RY, Ki EY, et al. Intraoperative Examination of Sentinel Lymph Nodes by Ultrarapid Immunohistochemistry in Breast Cancer [J].Jpn J Clin Oncol,2006,36(8):489-493.
[30]Holm M, Paaschburg B, Balslev E, et al. Intraoperative immunohistochemistry staining of sentinel nodes in breast cancer:clinical and economical implications[J]. Breast,2008,17(4):372-375.
[31]Jylling AM, Lindebjerg J, Nielsen L, et al. Immunohistochemistry on Frozen Section of Sentinel Lymph Nodes in Breast Cancer With Improved Morphology and Blocking of Endogenous Peroxidase[J]. Appl Immunohistochem Mol Morphol,2008,16:482-484.
[32]Turner RR, Ollila DW, Stem S, et al. Optimal histopathologic examination of the sentinel lymph node for breast carcinoma staging[J]. Am J Surg Pathol, 1999,23:263.
[33]Nahrig J, Richter T, Kowolik J, et al. Comparison of different histopathological methods for the examination of sentinel lymph nodes in breast cancer[J]. Anticancer Res,2000,20:2209-2212.
[34]Ollila DB, Stitzenberg K. Breast cancer sentinel node metastases:histopathologic detection and clinical significance[J]. Cancer Control,2001,8(5):407-414.
[35]Viale G, Maiorano E, Mazzarol G, et al. Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma[J]. Cancer,2001,92:1378-1384.
[36]Kanngurn S, Chewatanakornkul S, Premprapha T, et al. Comparability of different pathologic protocols in sentinel lymph node evaluation:an analysis of two step-sectioning methods for the same patients with breast cancer[J]. Arch Pathol Lab Med.,2009,133(9):1437-1440.
[37]van Diest PJ, Peterse HL, Borgstein PJ, et al. Pathological investigation of sentinel lymph nodes[J], Eur J Nucl Med,1999,26(Suppl):S43-S49.
[38]Martin M, Veys I, Majjaj S, et al. Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes [J]. Eur J Surg Oncol,2009,35(4):387-392.
[39]Blumencranz P, Whitworth PW, Deck K, et al. Sentinel node staging for breast cancer:intraoperative molecular pathology overcomes conventional histologic sampling errors[J]. Am J Surg,2007,194:426-432.
[40]Julian TB, Blumencranz P, Deck K, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer.[J]. J Clin Oncol,2008,26(20):3338-3345.
[41]Viale G, Dell'Orto P, Biasi MO, et al. comparative evaluation of an Extensive Histopathologic Examination and a Real-Time Reverse-Transcription-Polymerase chain Reaction Assay for Mammaglobin and Cytokeratin 19 on Axillary Sentinel Lymph Nodes of Breast Carcinoma Patients[J]. Ann Surg,2008,247(1):136-142.
[42]Lefferts JA, Bartels CL, Tsongalis GJ. Molecular oncology:current trends in diagnostics[J]. Future Oncol,2008,4(1):61-70.
[43]Veys I, Durbecq V, Majjaj S, et al. Eighteen months clinical experience with the GeneSearch breast lymph node assay [J]. Am J Surg,2009,198(2):203-209.
[44]Tamaki Y, Akiyama F, Iwase T, et al. Molecular detection of lymph node metastases in breast cancer patients:results of a multicenter trial using the one-step nucleic acid amplification assay [J]. Clin Cancer Res, 2009,15(8):2879-2884.
[45]Schem C, Maass N, Bauerschlag DO, et al. One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group [J]. Virchows Arch, 2009,454(2):203-210.
[46]Tsujimoto M, Nakabayashi K, Yoshidome K, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients[J]. Clin Cancer Res,2007,13(16):4807-4816.
[47]Le Frere-Belda MA, Bats AS, Gillaizeau F, et al. Diagnostic performance of one-step nucleic acid amplification for intraoperative sentinel node metastasis detection in breast cancer patients[J]. Int J Cancer,2012,15;130(10):2377-2386.
[48]Osako T, Iwase T, Kimura K, et al. Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer:A comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology[J]. Cancer,2011,117(19):4365-4374.
[49]Snook KL, Layer GT, Jackson PA, et al. Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma[J]. Br J Surg, 2011,98(4):527-535.
[50]Feldman S, Krishnamurthy S, Gillanders W, et al. A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes[J]. Cancer,2011,117(12):2599-2607.
[51]Visser M, Jiwa M, Horstman A, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer[J]. Int J Cancer,2008,122(11):2562-2567.
[52]Bernet L, Cano R, Martinez M, et al. Diagnosis of the sentinel lymph node in breast cancer:a reproducible molecular method:a multicentric Spanish study[J]. Histopathology,2011,58(6):863-869.
[53]Reed J, Rosman M, Verbanac KM, et al. Prognostic Implications of Isolated Tumor Cells and Micrometastases in Sentinel Nodes of Patients with Invasive Breast Cancer:10-Year Analysis of Patients Enrolled in the Prospective East Carolina University/Anne Arundel Medical Center Sentinel Node Multicenter Study [J]. J Am Coll Surg,2009,208(3):334-340.
[54]Houvenaeghel G, Nos C, Mignotte H. Micrometastases in sentinel lymph node in a multicentric study:redictive factors of nonsentinel lymph node involvement[J]. J Clin Oncol,2006,24(12):1814-1822.
[55]Viale G, Maiorano E, Pruneri G. Predicting the risk for additional axillary metastases in patients with breast carcinoma and positive sentinel lymph node biopsy [J]. Ann Surg,2005,241(2):319-325.
[56]Rutgers EJ. Sentinel Node Biopsy:Interpretation and Management of Patients With Immunohistochemistry-Positive Sentinel Nodes and Those With Micrometastases[J]. J Clin Oncol,2008,26(5):698-702.
[57]Ludwig Breast Cancer Study Group. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. International (Ludwig) Breast Cancer Study Group[J]. Lancet,1990,335:1565-1568.
[58]Cox CE, Kiluk JV, Riker AL. Significance of sentinel node micrometastases in human breast cancer[J]. J Am Coll Surg,2008,206:261-268.
[59]Marinho VF, Zagury MS, Caldeira LG, et al. Relationship between histologic features of primary breast carcinomas and axillary lymph node micrometastases: Detection and prognostic significance[J]. Appl Immunohistochem Mol Morphol, 2006,14(4):426-431.
[60]Bulte CS, van der Heiden-van der Loo M, Hennipman A. Axillary recurrence rate after tumour negative and micrometastatic positive sentinel node procedures in breast cancer patients, a population based multicenter study [J]. Eur J Surg Oncol, 2009,35(l):25-31.
[61]Hansen NM, Grube B, Ye X, et al. Impact of micrometastases in the sentinel node of patients with invasive breast cancer[J]. J Clin Oncol,2009,27(28):4679-4684.
[62]Onishi T, Jinno H, Takahashi M, et al. Non-sentinel lymph node status and prognosis of breast cancer patients with micrometastatic sentinel lymph nodes[J]. Eur Surg Res,2010,45(3-4):344-349.
[63]Langer I, Marti WR, Guller U, et al. Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy[J]. Ann Surg, 2005,241(1):152-158.
[64]Wasif N, Ye X, Giuliano AE. Survey of ASCO members on management of sentinel node micrometastases in breast cancer:variation in treatment recommendations according to specialty [J]. Ann Surg Oncol, 2009,16(9):2442-2449.
[65]Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases:the American College of Surgeons Oncology Group Z0011 randomized trial [J]. Ann Surg,2010,252(3):426-432,432-433.
[66]Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis:a randomized clinical trial[J]. JAMA,2011,305(6):569-575.
[67]Olsen SB, Amr B, Omar A, et al. Are the Findings of ASOCOG Z0011 Applicable to District General Hospital Breast Unit-And How Should They Change Our Practice?:San Antonio Breast Cancer Symposium,San Antonio Texas USA, December 6-10,2011[C].Berlin:Springer,c2000.
[68]Schwartz GF, Solin LJ, Olivotto IA, et al. The consensus conference on the treatment of in situ ductal carcinoma of the breast, April 22-25,1999[J]. Breast, 2000,9(4):177-186.
[69]Cox CE, Nguyen K, Gray RJ, et al. Importance of lymphatic mapping in ductal carcinoma in situ (DCIS):why map DCIS?[J]. Am Surg,2001,67(6):513-519, 519-521.
[70]Cserni G. Sentinel lymph node biopsy as a tool for the staging of ductal carcinoma in situ in patients with breast carcinoma[J]. Surg Today, 2002,32(2):99-103.
[71]Dominguez FJ, Golshan M, Black DM, et al. Sentinel node biopsy is important in mastectomy for ductal carcinoma in situ[J]. Ann Surg Oncol, 2008,15(1):268-273.
[72]Farkas EA, Stolier AJ, Teng SC, et al. An argument against routine sentinel node mapping for DCIS[J]. Am Surg,2004,70:13-17.
[73]Intra M, Veronesi P, Mazzarol G, et al. Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast[J]. Arch Surg, 2003,138(3):309-313.
[74]Katz A, Gage I, Evans S, et al. Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer[J]. Am J Surg, 2006,191(6):761-766.
[75]Kelly TA, Kim JA, Patrick R, et al. Axillary lymph node metastases in patients with a final diagnosis of ductal carcinoma in situ[J]. Am J Surg, 2003,186(4):368-370.
[76]Mabry H, Giuliano AE, Silverstein MJ. What is the value of axillary dissection or sentinel node biopsy in patients with ductal carcinoma in situ?[J]. Am J Surg, 2006,192(4):455-457.
[77]Sakr R, Barranger E, Antoine M, et al. Ductal carcinoma in situ:value of sentinel lymph node biopsy[J]. J Surg Oncol,2006,94(5):426-430.
[78]Veronesi P, Intra M, Vento AR, et al. Sentinel lymph node biopsy for localised ductal carcinoma in situ?[J]. Breast,2005,14(6):520-522.
[79]Zavagno G, Carcoforo P, Marconato R, et al. Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast[J]. BMC Cancer,2005,5:28.
[80]Sakr R, Antoine M, Barranger E, et al. Value of sentinel lymph node biopsy in breast ductal carcinoma in situ upstaged to invasive carcinoma[J]. Breast J, 2008,14(1):55-60.
[81]van la Parra RF, Ernst MF, Barneveld PC, et al. The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast[J]. Eur J Surg Oncol,2008,34(6):631-635.
[82]Klauber-DeMore N, Tan LK, Liberman L, et al. Sentinel lymph node biopsy:is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?[J]. Ann Surg Oncol,2000,7(9):636-642.
[83]D'Eredita G, Giardina C, Napoli A, et al. Sentinel lymph node biopsy in patients with pure and high-risk ductal carcinoma in situ of the breast.[J]. Tumori, 2009,95(6):706-711.
[84]DeSantis C, Siegel R, Bandi P, et al. Breast cancer statistics,2011[J]. CA Cancer J Clin,2011,61 (6):409-418.
[85]van de Vijver MJ, He YD, Van'T VL, et al. A gene-expression signature as a predictor of survival in breast cancer[J]. N Engl J Med,2002,347(25):1999-2009.
[86]Chelouche-Lev D, Kluger HM, Berger AJ, et al. alphaB-crystallin as a marker of lymph node involvement in breast carcinoma. [J]. Cancer, 2004,100(12):2543-2548.
[87]房爱菊,孟斌,刘文君,等α-B crystallin在乳腺浸润性导管癌中的表达及意义[J].山东大学学报(医学版),2008,46(3)：280-283.
[88]Moyano JV, Evans JR, Chen F, et al. AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer.[J]. J Clin Invest, 2006,116(1):261-270.
[89]Magnaldo T, Bernerd F, Darmon M. Galectin-7, a human 14-kDa S-lectin, specifically expressed in keratinocytes and sensitive to retinoic acid[J]. Dev Biol,1995,168(2):259-271.
[90]Timmons PM, Colnot C, Cail I, et al. Expression of galectin-7 during epithelial development coincides with the onset of stratification[J]. Int J Dev Biol, 1999,43(3):229-235.
[91]Kuwabara I, Kuwabara Y, Yang RY, et al. Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release[J]. J Biol Chem,2002,277(5):3487-3497.
[92]Bernerd F, Sarasin A, Magnaldo T. Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes[J]. Proc Natl Acad SciUS A,1999,96(20):11329-11334.
[93]Ueda S, Kuwabara I, Liu FT. Suppression of tumor growth by galectin-7 gene transfer[J]. Cancer Res,2004,64(16):5672-5676.
[94]Kopitz J, Andre S, von Reitzenstein C, et al. Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells[J]. Oncogene,2003,22(40):6277-6288.
[95]Lu J, Pei H, Kaeck M, et al. Gene expression changes associated with chemically induced rat mammary carcinogenesis[J]. Mol Carcinog,1997,20(2):204-215.
[96]Rorive S, Eddafali B, Fernandez S, et al. Changes in galectin-7 and cytokeratin-19 expression during the progression of malignancy in thyroid tumors: diagnostic and biological implications[J]. Mod Pathol,2002,15(12):1294-1301.
[97]Chen J, He QY, Yuen AP, et al. Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis[J]. Proteomics, 2004,4(8):2465-2475.
[98]Zhu X, Ding M, Yu ML, et al. Identification of galectin-7 as a potential biomarker for esophageal squamous cell carcinoma by proteomic analysis[J]. BMC Cancer,2010,10:290.
[99]Demers M, Rose AA, Grosset AA, et al. Overexpression of galectin-7, a myoepithelial cell marker, enhances spontaneous metastasis of breast cancer cells[J]. Am J Pathol,2010,176(6):3023-3031.
[2]Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer [J]. Oncologist,2004,9(6):606-616.
[3]Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases[J]. Cancer,1989,63(1):181-187.
[4]Warmuth MA, Bowen G, Prosnitz LR, et al. Complications of axillary lymph node dissection for carcinoma of the breast:a report based on a patient survey [J]. Cancer,1998,83(7):1362-1368.
[5]Kuehn T, Klauss W, Darsow M, et al. Long-term morbidity following axillary dissection in breast cancer patients--clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors [J]. Breast Cancer Res Treat,2000,64(3):275-286.
[6]Petrek JA, Senie RT, Peters M, et al. Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis[J]. Cancer,2001,92(6):1368-1377.
[7]Schrenk P, Rieger R, Shamiyeh A, et al. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma[J]. Cancer,2000,88:608-614.
[8]Silberman AW, McVay C, Cohen JS, et al. Comparative morbidity of axillary lymph node dissection and the sentinel lymph node technique:implications for patients with breast cancer[J]. Ann Surg,2004,240(1):1-6.
[9]Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial[J]. J Natl Cancer Inst,2006,98(9):599-609.
[10]Latosinsky S, Dabbs K, Moffat F. Canadian Association of General Surgeons and American College of Surgeons Evidence-Based Reviews in Surgery.27. Quality-of-life outcomes with sentinel node biopsy versus standard axillary treatment in patients with operable breast cancer. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial[J]. Can J Surg,2008,51(6):483-485.
[11]ASCO guideline recommendations for sentinel lymph node biopsy in early stage breast cancer[J]. J Clin Oncol,2005,23:7703-7720.
[12]Blumencranz P, Whitworth PW, Deck K, et al. Sentinel node staging for breast cancer:intraoperative molecular pathology overcomes conventional histologic sampling errors[J]. Am J Surg,2007,194:426-432.
[13]Julian TB, Blumencranz P, Deck K, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer [J]. J Clin Oncol,2008,26(20):3338-3345.
[14]Tamaki Y, Akiyama F, Iwase T, et al. Molecular detection of lymph node metastases in breast cancer patients:results of a multicenter trial using the one-step nucleic acid amplification assay [J]. Clin Cancer Res, 2009,15(8):2879-2884.
[15]Schem C, Maass N, Bauerschlag DO, et al. One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group[J]. Virchows Arch, 2009,454(2):203-210.
[16]Visser M, Jiwa M, Horstman A, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer[J]. Int J Cancer,2008,122(11):2562-2567.
[17]Sakr R, Antoine M, Barranger E, et al. Value of sentinel lymph node biopsy in breast ductal carcinoma in situ upstaged to invasive carcinoma.[J]. Breast J, 2008,14(1):55-60.
[18]Schwartz GF, Solin LJ, Olivotto IA, et al. The consensus conference on the treatment of in situ ductal carcinoma of the breast, April 22-25,1999[J]. Breast, 2000,9(4):177-186.
[19]Morrow M, Venta L, Stinson T, et al. Prospective comparison of stereotactic core biopsy and surgical excision as diagnostic procedures for breast cancer patients [J]. Ann Surg,2001,233(4):537-541.
[20]Klauber-DeMore N, Tan LK, Liberman L, et al. Sentinel lymph node biopsy:is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?[J]. Ann Surg Oncol,2000,7(9):636-642.
[21]Sakr R, Barranger E, Antoine M, et al. Ductal carcinoma in situ:value of sentinel lymph node biopsy[J]. J Surg Oncol,2006,94(5):426-430.
[22]D'Eredita G, Giardina C, Napoli A, et al. Sentinel lymph node biopsy in patients with pure and high-risk ductal carcinoma in situ of the breast.[J]. Tumori, 2009,95(6):706-711.
[23]Sener SF, Winchester DJ, Martz CH, et al. Lymphedema after sentinel lymphadenectomy for breast carcinoma[J]. Cancer,2001,92(4):748-752.
[24]Kuerer HM, Wayne JD, Ross MI. Anaphylaxis during breast cancer lymphatic mapping[J]. Surgery,2001,129(1):119-120.
[25]Aydogan F, Celik V, Uras C, et al. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2008,195(2):277-278.
[26]Saft S, Sarap M. Anaphylaxis during sentinel lymph node mapping[J]. JAAPA, 2007,20(9):26-28.
[27]Thevarajah S, Huston TL, Simmons RM. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2005,189(2):236-239.
[28]Chelouche-Lev D, Kluger HM, Berger AJ, et al. alphaB-crystallin as a marker of lymph node involvement in breast carcinoma[J]. Cancer, 2004,100(12):2543-2548.
[29]Saussez S, Kiss R. Galectin-7[J]. Cell Mol Life Sci,2006,63(6):686-697.
[30]Demers M, Rose AA, Grosset AA, et al. Overexpression of galectin-7, a myoepithelial cell marker, enhances spontaneous metastasis of breast cancer cells[J]. Am J Pathol,2010,176(6):3023-3031.
[1]Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol,2005,23(30):7703-7720.
[2]Motomura K, Nagumo S, Komoike Y, et al. Accuracy of imprint cytology for intraoperative diagnosis of sentinel node metastases in breast cancer [J]. Ann Surg, 2008,247(5):839-842.
[3]Tew K, Irwig L, Matthews A, et al. Meta-analysis of sentinel node imprint cytology in breast cancer[J]. Br J Surg,2005,92(9):1068-1080.
[4]Perez-Sanchez VM, Vela-Chavez TA, Villarreal-Colin P, et al. Intraoperative touch imprint cytology of sentinel lymph nodes in breast cancer:experience at a tertiary care center in Mexico[J]. Med Oncol,2010,27(2):233-236.
[5]Creager AJ, Geisinger KR, Shiver SA, et al. Intraoperative evaluation of sentinel lymph nodes for metastatic breast carcinoma by imprint cytology[J]. Mod Pathol, 2002,15(11):1140-1147.
[6]Cox C, Centeno B, Dickson D, et al. Accuracy of intraoperative imprint cytology for sentinel lymph node evaluation in the treatment of breast carcinoma[J]. Cancer,2005,105(1):13-20.
[7]Langer I, Guller U, Berclaz G, et al. Accuracy of frozen section of sentinel lymph nodes:a prospective analysis of 659 breast cancer patients of the Swiss multicenter study [J]. Breast Cancer Res Treat,2009,113(1):129-136.
[8]Creager AJ, Geisinger KR. Intraoperative Evaluation of Sentinel Lymph Nodes for Breast Carcinoma:Current Methodologies [J]. Adv Anat Pathol, 2002,9(4):233-243.
[9]Noriaki W, Shigeru I, Takahiro H, et al. Evaluation of Intraoperative Frozen Section Diagnosis of Sentinel Lymph Nodes in Breast Cancer[J]. Jpn J Clin Oncol,2004,34(3):1113-17.
[10]van de Vrande S, Meijer J, Rijnders A, et al. The value of intraoperative frozen section examination of sentinel lymph nodes in breast cancer [J]. Eur J Surg Oncol, 2009,35(3):276-280.
[11]Chao C. The use of frozen section and immunohistchemistry for sentinel lymph node biopsy in breast cancer[J]. Am Surg,2004,70(5):414-419.
[12]Bernstein JL, Godbold JH, Raptis G, et al. Identification of mammaglobin as a novel serum marker for breast cancer [J]. Clin Cancer Res, 2005,11(18):6528-6535.
[13]Zehentner BK, Carter D. Mammaglobin:a candidate diagnostic marker for breast cancer[J]. Clin Biochem,2004,37(4):249-257.
[14]Schoenfeld A, Kruger KH, Gomm J, et al. The detection of micrometastases in the peripheral blood and bone marrow of patients with breast cancer using immunohistochemistry and reverse transcriptase polymerase chain reaction for keratin 19[J]. Eur J Cancer,1997,33(6):854-861.
[15]Backus J, Laughlin T, Wang Y, et al. Identification and characterization of optimal gene expression markers for detection of breast cancer metastasis[J]. J Mol Diagn,2005,7(3):327-336.
[16]Julian TB, Blumencranz P, Deck K, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer [J]. J Clin Oncol,2008,26(20):3338-3345.
[17]Tamaki Y, Akiyama F, Iwase T, et al. Molecular detection of lymph node metastases in breast cancer patients:results of a multicenter trial using the one-step nucleic acid amplification assay [J]. Clin Cancer Res, 2009,15(8):2879-2884.
[18]Schem C, Maass N, Bauerschlag DO, et al. One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group[J]. Virchows Arch, 2009,454(2):203-210.
[19]Visser M, Jiwa M, Horstman A, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer[J]. Int J Cancer,2008,122(11):2562-2567.
[20]Cserni G, Bianchi S, Vezzosi V, et al. Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions [J]. Eur J Cancer, 2008,44(15):2185-2191.
[21]Osako T, Iwase T, Kimura K, et al. Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer:A comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology [J]. Cancer,2011.
[22]Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol,2005,23(30):7703-7720.
[23]Reed J, Rosman M, Verbanac KM, et al. Prognostic Implications of Isolated Tumor Cells and Micrometastases in Sentinel Nodes of Patients with Invasive Breast Cancer:10-Year Analysis of Patients Enrolled in the Prospective East Carolina University/Anne Arundel Medical Center Sentinel Node Multicenter Study[J]. J Am Coll Surg,2009,208(3):334-340.
[24]Cox CE, Kiluk JV, Riker AL. Significance of sentinel node micrometastases in human breast cancer[J]. J Am Coll Surg,2008,206:261-268.
[25]Marinho VF, Zagury MS, Caldeira LG, et al. Relationship between histologic features of primary breast carcinomas and axillary lymph node micrometastases: Detection and prognostic significance [J]. Appl Immunohistochem Mol Morphol, 2006,14(4):426-431.
[26]Bulte CS, van der Heiden-van der Loo M, Hennipman A. Axillary recurrence rate after tumour negative and micrometastatic positive sentinel node procedures in breast cancer patients, a population based multicenter study [J]. Eur J Surg Oncol, 2009,35(1):25-31.
[27]Hansen NM, Grube B, Ye X, et al. Impact of micrometastases in the sentinel node of patients with invasive breast cancer[J]. J Clin Oncol,2009,27(28):4679-4684.
[28]Onishi T, Jinno H, Takahashi M, et al. Non-sentinel lymph node status and prognosis of breast cancer patients with micrometastatic sentinel lymph nodes[J]. Eur Surg Res,2010,45(3-4):344-349.
[29]Langer I, Marti WR, Guller U, et al. Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy [J]. Ann Surg, 2005,241(1):152-158.
[30]Wasif N, Ye X, Giuliano A E. Survey of ASCO members on management of sentinel node micrometastases in breast cancer:variation in treatment recommendations according to specialty [J]. Ann Surg Oncol, 2009,16(9):2442-2449.
[31]Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases:the American College of Surgeons Oncology Group Z0011 randomized trial[J]. Ann Surg,2010,252(3):426-432,432-433.
[32]Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis:a randomized clinical trial[J]. JAMA,2011,305(6):569-575.
[33]Cserni G. Axillary staging of breast cancer and the sentinel node[J]. J Clin Pathol, 2000,53(10):733-741.
[34]Turner RR, Ollila DW, Stern S, et al. Optimal histopathologic examination of the sentinel lymph node for breast carcinoma staging[J]. Am J Surg Pathol, 1999,23(3):263-267.
[35]Cserni G, Amendoeira I, Apostolikas N, et al. Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology[J]. J Clin Pathol,2004,57(7):695-701.
[36]Blumencranz P, Whitworth PW, Deck K, et al. Sentinel node staging for breast cancer:intraoperative molecular pathology overcomes conventional histologic sampling errors[J]. Am J Surg,2007,194:426-432.
[37]Julian TB, Blumencranz P, Deck K, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer.[J]. J Clin Oncol,2008,26(20):3338-3345.
[38]Martin Martinez MD, Veys I, Majjaj S, et al. Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes[J]. Eur J Surg Oncol,2009,35(4):387-392.
[39]Viale G, Dell'Orto P, Biasi MO, et al. comparative evaluation of an Extensive Histopathologic Examination and a Real-Time Reverse-Transcription-Polymerase chain Reaction Assay for Mammaglobin and Cytokeratin 19 on Axillary Sentinel Lymph Nodes of Breast Carcinoma Patients[J]. Ann Surg,2008,247(1):136-142.
[40]Lefferts JA, Bartels CL, Tsongalis GJ. Molecular oncology:current trends in diagnostics [J]. Future Oncol,2008,4(1):61-70.
[41]Veys I, Durbecq V, Majjaj S, et al. Eighteen months clinical experience with the GeneSearch breast lymph node assay [J]. Am J Surg,2009,198(2):203-209.
[42]Chen JJ, Yang BL, Zhang JX, et al. The evaluation and optimization of intraoperative touch imprint cytology for sentinel lymph nodes in early-stage breast cancer in China[J]. World J Surg,2010,34(10):2325-2332.
[43]Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging manual (7th ed)[M]. New York:Springer,2010.
[44]Guillanders WE, Mikhitarian K, Hebert R, et al. Molecular detection of micrometastatic breast cancer in histopathologynegative axillary lymph nodes correlates with traditional predictors of prognosis[J]. Ann Surg, 2004,239:828-840.
[45]Liberman L. Pathologic analysis of sentinel lymph nodes in breast carcinoma[J]. Cancer,2000,88:971-977.
[46]Ouellette J, Richard D, Maicas E. Correction of RT-PCR for mammaglobin genes,MGB1 and MGB2, identifies breast cancer micrometastases in sentinel lymph nodes[J]. Am J Clin Pathol,2004,122:813.
[47]Valeria D, Daniela A, Fernando P, et al. Sentinel Lymph Node Molecular Pathology in Breast Carcinoma[J]. Diagn Mol Pathol,2008,17:214-219.
[48]Ouellette RJ, Richard D, Maicas E. RT-PCR for mammaglobin genes, MGB1 and MGB2, identifies breast cancer micrometastases in sentinel lymph nodes [J]. Am J Clin Pathol,2004,121:637-643.
[49]Zehentner B, Persing D, Deme A, et al. Mammaglobin as a novel breast cancer biomarker:multigene reverse transcription PCR assay and sandwich ELISA[J]. Clin Chem,2004,50:2069-2076.
[50]Tsujimoto M, Nakabayashi K, Yoshidome K, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients [J]. Clin Cancer Res,2007,13(16):4807-4816.
[51]Le Frere-Belda MA, Bats AS, Gillaizeau F, et al. Diagnostic performance of one-step nucleic acid amplification for intraoperative sentinel node metastasis detection in breast cancer patients[J]. Int J Cancer,2012,130(10):2377-2386.
[52]Snook KL, Layer GT, Jackson PA, et al. Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma[J]. Br J Surg, 2011,98(4):527-535.
[53]Feldman S, Krishnamurthy S, Gillanders W, et al. A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes[J]. Cancer,2011,117(12):2599-2607.
[54]Bernet L, Cano R, Martinez M, et al. Diagnosis of the sentinel lymph node in breast cancer:a reproducible molecular method:a multicentric Spanish study[J]. Histopathology,2011,58(6):863-869.
[55]Turner RR, Ollila DW, Stem S, et al. Optimal histopathologic examination of the sentinel lymph node for breast carcinoma staging[J]. Am J Surg Pathol, 1999,23(3):263.
[56]Nahrig J, Richter T, Kowolik J, et al. Comparison of different histopathological methods for the examination of sentinel lymph nodes in breast cancer [J]. Anticancer Res,2000,20(3B):2209-2212.
[57]Viale G, Maiorano E, Mazzarol G, et al. Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma[J]. Cancer,2001,92(6):1378-1384.
[58]Kanngurn S, Chewatanakornkul S, Premprapha T, et al. Comparability of different pathologic protocols in sentinel lymph node evaluation:an analysis of two step-sectioning methods for the same patients with breast cancer[J]. Arch Pathol Lab Med.,2009,133(9):1437-1440.
[59]van Diest PJ, Peterse HL, Borgstein PJ, et al. Pathological investigation of sentinel lymph nodes[J]. Eur J Nucl Med,1999,26(Suppl):S43-S49.
[60]Schwartz GF, Giuliano AE, Veronesi U. Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast April 19 to 22,2001, Philadelphia, Pennsylvania[J]. Hum Pathol,2002,33(6):579-589.
[61]Cserni G, Amendoeira I, Apostolikas N, et al. Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines[J]. Eur J Cancer,2003,39(12):1654-1667.
[62]Turner RR, Donald LW, Gabor C, et al. Nodal Stage Classification for Breast Carcinoma:Improving Interobserver Reproducibility Through Standardized Histologic Criteria and Image-Based Training[J]. J Clin Oncol,2008,26:258-265.
[63]Cserin G, Sapino A, Decker T. Discriminating between micrometastases and isolated tumor cells in a regional and institutional setting[J].The Breast, 2006,15:347-354.
[64]Rutgers EJ. Sentinel Node Biopsy:Interpretation and Management of Patients With Immunohistochemistry-Positive Sentinel Nodes and Those With Micrometastases [J]. J Clin Oncol,2008,26(5):698-702.
[65]Ludwig breast cancer study group. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. International (Ludwig) Breast Cancer Study Group[J]. Lancet,1990,335(8705):1565-1568.
[66]Houvenaeghel G, Nos C, Mignotte H. Micrometastases in sentinel lymph node in a multicentric study:redictive factors of nonsentinel lymph node involvement [J]. J Clin Oncol,2006,24(12):1814-1822.
[67]Viale G, Maiorano E, Pruneri G. Predicting the risk for additional axillary metastases in patients with breast carcinoma and positive sentinel lymph node biopsy[J]. Ann Surg,2005,241(2):319-325.
[1]Schwartz GF, Solin LJ, Olivotto IA, et al. The consensus conference on the treatment of in situ ductal carcinoma of the breast, April 22-25,1999[J]. Breast, 2000,9(4):177-186.
[2]Cox CE, Nguyen K, Gray RJ, et al. Importance of lymphatic mapping in ductal carcinoma in situ (DCIS):why map DCIS?[J]. Am Surg,2001,67(6):513-519, 519-521.
[3]Cserni G. Sentinel lymph node biopsy as a tool for the staging of ductal carcinoma in situ in patients with breast carcinoma[J]. Surg Today, 2002,32(2):99-103.
[4]Dominguez FJ, Golshan M, Black DM, et al. Sentinel node biopsy is important in mastectomy for ductal carcinoma in situ[J]. Ann Surg Oncol, 2008,15(1):268-273.
[5]Farkas EA, Stolier AJ, Teng SC, et al. An argument against routine sentinel node mapping for DCIS[J]. Am Surg,2004,70:13-17.
[6]Intra M, Veronesi P, Mazzarol G, et al. Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast[J]. Arch Surg, 2003,138(3):309-313.
[7]Katz A, Gage I, Evans S, et al. Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer[J]. Am J Surg, 2006,191(6):761-766.
[8]Kelly TA, Kim JA, Patrick R, et al. Axillary lymph node metastases in patients with a final diagnosis of ductal carcinoma in situ[J]. Am J Surg, 2003,186(4):368-370.
[9]Mabry H, Giuliano AE, Silverstein MJ. What is the value of axillary dissection or sentinel node biopsy in patients with ductal carcinoma in situ?[J]. Am J Surg, 2006,192(4):455-457.
[10]Sakr R, Antoine M, Barranger E, et al. Value of sentinel lymph node biopsy in breast ductal carcinoma in situ upstaged to invasive carcinoma[J]. Breast J, 2008,14(1):55-60.
[11]Veronesi P, Intra M, Vento AR, et al. Sentinel lymph node biopsy for localised ductal carcinoma in situ?[J]. Breast,2005,14(6):520-522.
[12]Zavagno G, Carcoforo P, Marconato R, et al. Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast[J]. BMC Cancer,2005,5:28.
[13]Sakr R, Barranger E, Antoine M, et al. Ductal carcinoma in situ:value of sentinel lymph node biopsy[J]. J Surg Oncol,2006,94(5):426-430.
[14]van la Parra RF, Ernst MF, Barneveld PC, et al. The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast[J]. Eur J Surg Oncol,2008,34(6):631-635.
[15]Klauber-DeMore N, Tan LK, Liberman L, et al. Sentinel lymph node biopsy:is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?[J]. Ann Surg Oncol,2000,7(9):636-642.
[16]D'Eredita G, Giardina C, Napoli A, et al. Sentinel lymph node biopsy in patients with pure and high-risk ductal carcinoma in situ of the breast.[J]. Tumori, 2009,95(6):706-711.
[17]van Rijk M C, Peterse J L, Nieweg O E, et al. Additional axillary metastases and stage migration in breast cancer patients with micrometastases or submi-crometastases in sentinel lymph nodes[J]. Cancer,2006,107:467-471.
[18]Cserni G, Bianchi S, Vezzosi V, et al. Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions[J]. Eur J Cancer, 2008,44(15):2185-2191.
[19]American Joint Committee On Cancer. AJCC cancer staging manual [M],7 th ed. New York:Springer,2010:354.
[20]Fentiman IS.8. The dilemma of in situ carcinoma of the breast[J]. Int J Clin Pract, 2001,55(10):680-683.
[21]Ernster VL, Ballard-Barbash R, Barlow WE, et al. Detection of ductal carcinoma in situ in women undergoing screening mammography[J]. J Natl Cancer Inst, 2002,94(20):1546-1554.
[22]Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases[J]. Cancer,1989,63(1):181-187.
[23]Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer[J]. Oncologist,2004,9(6):606-616.
[24]Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol,2005,23(30):7703-7720.
[25]Warmuth MA, Bowen G, Prosnitz LR, et al. Complications of axillary lymph node dissection for carcinoma of the breast:a report based on a patient survey[J]. Cancer,1998,83(7):1362-1368.
[26]Kuehn T, Klauss W, Darsow M, et al. Long-term morbidity following axillary dissection in breast cancer patients--clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors [J]. Breast Cancer Res Treat,2000,64(3):275-286.
[27]Petrek JA, Senie RT, Peters M, et al. Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis[J]. Cancer,2001,92(6):1368-1377.
[28]National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology-Breast Cancer Guideline 2011.
[29]Goyal A, Douglas-Jones A, Monypenny I, et al. Is there a role of sentinel lymph node biopsy in ductal carcinoma in situ?:analysis of 587 cases [J]. Breast Cancer Res Treat,2006,98(3):311-314.
[30]Ansari B, Ogston SA, Purdie CA, et al. Meta-analysis of sentinel node biopsy in ductal carcinoma in situ of the breast [J]. Br J Surg,2008,95(5):547-554.
[31]Pendas S, Dauway E, Giuliano R, et al. Sentinel node biopsy in ductal carcinoma in situ patients[J]. Ann Surg Oncol,2000,7(1):15-20.
[32]Schrenk P, Rieger R, Shamiyeh A, et al. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma[J]. Cancer,2000,88(3):608-614.
[33]Sener SF, Winchester DJ, Martz CH, et al. Lymphedema after sentinel lymphadenectomy for breast carcinoma[J]. Cancer,2001,92(4):748-752.
[34]Kuerer HM, Wayne JD, Ross MI. Anaphylaxis during breast cancer lymphatic mapping[J]. Surgery,2001,129(1):119-120.
[35]Aydogan F, Celik V, Uras C, et al. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2008,195(2):277-278.
[36]Saft S, Sarap M. Anaphylaxis during sentinel lymph node mapping[J]. JAAPA, 2007,20(9):26-28.
[37]Thevarajah S, Huston TL, Simmons RM. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2005,189(2):236-239.
[38]Yen TW, Hunt KK, Ross MI, et al. Predictors of invasive breast cancer in patients with an initial diagnosis of ductal carcinoma in situ:a guide to selective use of sentinel lymph node biopsy in management of ductal carcinoma in situ[J]. J Am Coll Surg,2005,200(4):516-526.
[39]Intra M, Brito J A D, Soteldo J, et al. Sentinel Lymph Node Biopsy in Intraductal Carcinoma of the Breast with Microinvasion[J]. Intl J Cancer Res,2005,1(1):1-4.
[40]Intra M, Zurrida S, Maffini F, et al. Sentinel lymph node metastasis in microinvasive breast cancer[J]. Ann Surg Oncol,2003,10(10):1160-1165.
[41]Moran CJ, Kell MR, Flanagan FL, et al. Role of sentinel lymph node biopsy in high-risk ductal carcinoma in situ patients[J]. Am J Surg,2007,194(2):172-175.
[42]Moran CJ, Kell MR, Kerin MJ. The role of sentinel lymph node biopsy in ductal carcinoma in situ[J]. Eur J Surg Oncol,2005,31 (10):1105-1111.
[43]Moore KH, Sweeney KJ, Wilson ME, et al. Outcomes for women with ductal carcinoma-in-situ and a positive sentinel node:a multi-institutional audit[J]. Ann Surg Oncol,2007,14(10):2911-2917.
[44]Huo L, Sneige N, Hunt KK, et al. Predictors of invasion in patients with core-needle biopsy-diagnosed ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy in ductal carcinoma in situ[J]. Cancer,2006,107(8):1760-1768.
[45]King TA, Farr GJ, Cederbom GJ, et al. A mass on breast imaging predicts coexisting invasive carcinoma in patients with a core biopsy diagnosis of ductal carcinoma in situ[J]. Am Surg,2001,67(9):907-912.
[46]Renshaw AA. Predicting invasion in the excision specimen from breast core needle biopsy specimens with only ductal carcinoma in situ[J]. Arch Pathol Lab Med,2002,126(1):39-41.
[47]Silver SA, Tavassoli FA. Mammary ductal carcinoma in situ with microinvasion[J]. Cancer,1998,82(12):2382-2390.
[48]Pimiento JM, Lee MC, Esposito NN, et al. Role of axillary staging in women diagnosed with ductal carcinoma in situ with microinvasion[J].J Oncol Pract, 2011,7(5):309-313.
[49]Adamovich TL, Simmons RM. Ductal carcinoma in situ with microinvasion[J]. Am J Surg,2003,186(2):112-116.
[50]Silverstein MJ, Lagios MD. Ductal carcinoma in situ with microinvasion[M]//MJ S. Ductal Carcinoma in Situ of the Breast. Philadelphia:Lippincott Williams and Wilkins,2002:557-562.
[51]de Mascarel I, MacGrogan G, Mathoulin-Pelissier S, et al. Breast ductal carcinoma in situ with microinvasion:a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas[J]. Cancer,2002,94(8):2134-2142.
[52]Prasad ML, Osborne MP, Giri DD, et al. Microinvasive carcinoma (Tlmic) of the breast:clinicopathologic profile of 21 cases[J]. Am J Surg Pathol, 2000,24(3):422-428.
[53]Yang M, Moriya T, Oguma M, et al. Microinvasive ductal carcinoma (Tlmic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases[J]. Pathol Int,2003,53(7):422-428.
[54]Vieira CC, Mercado CL, Cangiarella JF, et al. Microinvasive ductal carcinoma in situ:clinical presentation, imaging features, pathologic findings, and outcome[J]. Eur J Radiol,2010,73(1):102-107.
[55]Zavagno G, Belardinelli V, Marconato R, et al. Sentinel lymph node metastasis from mammary ductal carcinoma in situ with microinvasion[J]. Breast, 2007,16(2):146-151.
[56]Ko BS, Lim WS, Kim HJ, et al. Risk factor for axillary lymph node metastases in microinvasive breast cancer[J]. Ann Surg Oncol,2012,19(1):212-216.
[57]Parikh RR, Haffty BG, Lannin D, et al. Ductal Carcinoma In Situ with Microinvasion:Prognostic Implications, Long-Term Outcomes, and Role of Axillary Evaluation[J]. Int J Radiat Oncol Biol Phys,2010.
[58]Wong JH, Kopald KH, Morton DL. The impact of microinvasion on axillary node metastases and survival in patients with intraductal breast cancer[J]. Arch Surg, 1990,125(10):1298-1301,1301-1302.
[59]Solin LJ, Fowble BL, Yeh IT, et al. Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation[J]. Int J Radiat Oncol Biol Phys,1992,23(5):961-968.
[60]Rosner D, Lane WW, Penetrante R. Ductal carcinoma in situ with microinvasion. A curable entity using surgery alone without need for adjuvant therapy [J]. Cancer, 1991,67(6):1498-1503.
[61]Lara JF, Young SM, Velilla RE, et al. The relevance of occult axillary micrometastasis in ductal carcinoma in situ:a clinicopathologic study with long-term follow-up[J]. Cancer,2003,98(10):2105-2113.
[62]Murphy CD, Jones JL, Javid SH, et al. Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion?[J]. Am J Surg,2008,196(4):566-568.
[1]Wolmark N, Fisher B. Surgery in the primary treatment of breast cancer[J]. Breast Cancer Res Treat,1981,1 (4):339-348.
[2]Schrenk P, Rieger R, Shamiyeh A, et al. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma[J]. Cancer,2000,88:608-614.
[3]Husted Madsen A, Haugaard K, Soerensen J, et al. Arm morbidity following sentinel lymph node biopsy or axillary lymph node dissection:a study from the Danish Breast Cancer Cooperative Group [J]. Breast,2008,17(2):138-147
[4]Sener SF, Winchester DJ, Martz CH, et al. Lymphedema after sentinel lymphadenectomy for breast carcinoma[J]. Cancer,2001,92(4):748-752.
[5]Kuerer HM, Wayne JD, Ross MI. Anaphylaxis during breast cancer lymphatic mapping[J]. Surgery,2001,129(1):119-120.
[6]Aydogan F, Celik V, Uras C, et al. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2008,195(2):277-278.
[7]Saft S, Sarap M. Anaphylaxis during sentinel lymph node mapping[J]. JAAPA, 2007,20(9):26-28.
[8]Thevarajah S, Huston TL, Simmons RM. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer[J]. Am J Surg,2005,189(2):236-239.
[9]Bevilacqua JL, Kattan MW, Fey JV, et al. Doctor, what are my chances of having a positive sentinel node? A validated nomogram for risk estimation [J]. J Clin Oncol,2007,25(24):3670-3679.
[10]Chelouche-Lev D, Kluger HM, Berger AJ, et al. alphaB-crystallin as a marker of lymph node involvement in breast carcinoma. [J]. Cancer, 2004,100(12):2543-2548.
[11]Saussez S, Kiss R. Galectin-7[J]. Cell Mol Life Sci,2006,63(6):686-697.
[12]Demers M, Rose AA, Grosset AA, et al. Overexpression of galectin-7, a myoepithelial cell marker, enhances spontaneous metastasis of breast cancer cells[J]. Am J Pathol,2010,176(6):3023-3031.
[13]Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer:experience from a large study with long-term follow-up [J]. Histopathology,1991,19(5):403-410.
[14]Hutterer M, Knyazev P, Abate A, et al. Axl and growth arrest-specific gene 6 are frequently overexpressed in human gliomas and predict poor prognosis in patients with glioblastoma multiforme[J]. Clin Cancer Res,2008,14(1):130-138.
[15]Reschke M, Mihic-Probst D, van der Horst EH, et al. HER3 is a determinant for poor prognosis in melanoma[J]. Clin Cancer Res,2008,14(16):5188-5197.
[16]Remmele W, Schicketanz KH. Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS)[J]. Pathol Res Pract, 1993,189(8):862-866.
[17]DeSantis C, Siegel R, Bandi P, et al. Breast cancer statistics,2011[J]. CA Cancer J Clin,2011,61(6):409-418.
[18]van de Vijver MJ, He YD, Van'T VL, et al. A gene-expression signature as a predictor of survival in breast cancer[J]. N Engl J Med,2002,347(25):1999-2009.
[19]Dubin RA, Ally AH, Chung S, et al. Human alpha B-crystallin gene and preferential promoter function in lens[J]. Genomics,1990,7(4):594-601.
[20]Clark JI, Muchowski PJ. Small heat-shock proteins and their potential role in human disease[J]. Curr Opin Struct Biol,2000,10(1):52-59.
[21]Kamradt MC, Lu M, Werner ME, et al. The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3[J]. J Biol Chem,2005,280(12):11059-11066.
[22]Kamradt MC, Chen F, Sam S, et al. The small heat shock protein alpha B-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation[J]. J Biol Chem,2002,277(41):38731-38736.
[23]Kamradt MC, Chen F, Cryns VL. The small heat shock protein alpha B-crystallin negatively regulates cytochrome c-and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation[J]. J Biol Chem, 2001,276(19):16059-16063.
[24]Mao YW, Liu JP, Xiang H, et al. Human alphaA-and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis[J]. Cell Death Differ,2004,11 (5):512-526.
[25]Watanabe G, Kato S, Nakata H, et al. alphaB-crystallin:a novel p53-target gene required for p53-dependent apoptosis[J]. Cancer Sci,2009,100(12):2368-2375.
[26]Kase S, He S, Sonoda S, et al. alphaB-crystallin regulation of angiogenesis by modulation of VEGF.[J]. Blood,2010,115(16):3398-3406.
[27]Morrison LE, Whittaker RJ, Klepper RE, et al. Roles for alphaB-crystallin and HSPB2 in protecting the myocardium from ischemia-reperfusion-induced damage in a KO mouse model [J]. Am J Physiol Heart Circ Physiol, 2004,286(3):H847-H855.
[28]Vicart P, Caron A, Guicheney P, et al. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy[J]. Nat Genet,1998,20(1):92-95.
[29]Dabir DV, Trojanowski JQ, Richter-Landsberg C, et al. Expression of the small heat-shock protein alphaB-crystallin in tauopathies with glial pathology [J]. Am J Pathol,2004,164(1):155-166.
[30]Rekas A, Adda CG, Andrew AJ, et al. Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein:effects on amyloid fibril formation and chaperone activity [J]. J Mol Biol,2004,340(5):1167-1183.
[31]Raju I, Oonthonpan L, Abraham EC. Mutations in Human alphaA-Crystallin/sHSP Affect Subunit Exchange Interaction with alphaB-Crystallin[J]. PLoS One,2012,7(2):e31421.
[32]房爱菊,孟斌,刘文君，等a-B crystallin在乳腺浸润性导管癌中的表达及意义[J].山东大学学报(医学版),2008,46(3)：280-283.
[33]Moyano JV, Evans JR, Chen F, et al. AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer.[J]. J Clin Invest, 2006,116(1):261-270.
[34]Fan C, Oh DS, Wessels L, et al. Concordance among gene-expression-based predictors for breast cancer [J]. N Engl J Med,2006,355(6):560-569.
[35]Sitterding SM, Wiseman WR, Schiller CL, et al. AlphaB-crystallin:a novel marker of invasive basal-like and metaplastic breast carcinomas.[J]. Ann Diagn Pathol,2008,12(1):33-40.
[36]Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets[J]. Proc Natl Acad Sci U S A, 2003,100(14):8418-8423.
[37]Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications[J]. Proc Natl Acad Sci U S A,2001,98(19):10869-10874.
[38]Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours[J]. Nature,2000,406(6797):747-752.
[39]Livasy CA, Karaca G, Nanda R, et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma[J]. Mod Pathol,2006,19(2):264-271.
[40]Aoyama A, Steiger RH, Frohli E, et al. Expression of alpha B-crystallin in human brain tumors[J]. Int J Cancer,1993,55(5):760-764.
[41]Pinder SE, Balsitis M, Ellis 10, et al. The expression of alpha B-crystallin in epithelial tumours:a useful tumour marker?[J]. J Pathol,1994,174(3):209-215.
[42]Chin D, Boyle GM, Williams RM, et al. Alpha B-crystallin, a new independent marker for poor prognosis in head and neck cancer[J]. Laryngoscope, 2005,115(7):1239-1242.
[43]Bau DT, Tsai CW, Lin CC, et al. Association of alpha B-crystallin genotypes with oral cancer susceptibility, survival, and recurrence in Taiwan[J]. PLoS One, 2011,6(9):e16374.
[44]Magnaldo T, Bernerd F, Darmon M. Galectin-7, a human 14-kDa S-lectin, specifically expressed in keratinocytes and sensitive to retinoic acid[J]. Dev Biol,1995,168(2):259-271.
[45]Timmons PM, Colnot C, Cail I, et al. Expression of galectin-7 during epithelial development coincides with the onset of stratification [J]. Int J Dev Biol, 1999,43(3):229-235.
[46]Kuwabara I, Kuwabara Y, Yang RY, et al. Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release[J]. J Biol Chem,2002,277(5):3487-3497.
[47]Bernerd F, Sarasin A, Magnaldo T. Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes[J]. Proc Natl Acad Sci USA,1999,96(20):11329-11334.
[48]Ueda S, Kuwabara I, Liu FT. Suppression of tumor growth by galectin-7 gene transfer[J]. Cancer Res,2004,64(16):5672-5676.
[49]Kopitz J, Andre S, von Reitzenstein C, et al. Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells[J]. Oncogene,2003,22(40):6277-6288.
[50]Lu J, Pei H, Kaeck M, et al. Gene expression changes associated with chemically induced rat mammary carcinogenesis[J]. Mol Carcinog,1997,20(2):204-215.
[51]Rorive S, Eddafali B, Fernandez S, et al. Changes in galectin-7 and cytokeratin-19 expression during the progression of malignancy in thyroid tumors: diagnostic and biological implications[J]. Mod Pathol,2002,15(12):1294-1301.
[52]Chen J, He QY, Yuen AP, et al. Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis[J]. Proteomics, 2004,4(8):2465-2475.
[53]Zhu X, Ding M, Yu ML, et al. Identification of galectin-7 as a potential biomarker for esophageal squamous cell carcinoma by proteomic analysis[J]. BMC Cancer,2010,10:290.
[54]Lee JS, Lee Y, Jeon B, et al. EC-SOD induces apoptosis through COX-2 and galectin-7 in the epidermis[J]. J Dermatol Sci,2012,65(2):126-133.
[55]Saussez S, Decaestecker C, Lorfevre F, et al. Increased expression and altered intracellular distribution of adhesion/growth-regulatory lectins galectins-1 and -7 during tumour progression in hypopharyngeal and laryngeal squamous cell carcinomas [J]. Histopathology,2008,52(4):483-493.
[56]Demers M, Magnaldo T, St-Pierre Y. A novel function for galectin-7:promoting tumorigenesis by up-regulating MMP-9 gene expression[J]. Cancer Res, 2005,65(12):5205-5210.
[1]Lacroix M. Significance, detection and markers of disseminated breast cancer cells[J]. Endocr Relat Cancer,2006,13:1033-1067.
[2]Schrenk P, Rieger R, Shamiyeh A, et al. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast caicinoma[J]. Cancer,2000,88:608-614.
[3]Cabanas RM. Anatomy and biopsy of sentinel lymph nodes[J]. Urol Clin North Am,1992,19(2):267-276.
[4]Turner RR, Donald LW, Gabor C, et al. Nodal Stage Classification for Breast Carcinoma:Improving Interobserver Reproducibility Through Standardized Histologic Criteria and Image-Based Training[J]. J Clin Oncol,2008,26:258-265.
[5]Cserin G, Sapino A, Decker T. Discriminating between micrometastases and isolated tumor cells in a regional and institutional setting[J]. The Breast, 2006,15:347-354.
[6]Cserni G, Bianchi S, Vezzosi V, et al. Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions[J]. Eur J Cancer, 2008,44(15):2185-2191.
[7]Motomura K, Nagumo S, Komoike Y, et al. Accuracy of imprint cytology for intraoperative diagnosis of sentinel node metastases in breast cancer[J]. Ann Surg, 2008,247(5):839-842.
[8]Tew K, Irwig L, Matthews A, et al. Meta-analysis of sentinel node imprint cytology in breast cancer[J]. Br J Surg,2005,92(9):1068-1080.
[9]Chicken DW, Kocjan G, Falzon M, et al. Intraoperative touch imprint cytology for the diagnosis of sentinel lymph node metastases in breast cancer[J]. Br J Surg, 2006,93(5):572-576.
[10]Perez-Sanchez VM, Vela-Chavez TA, Villarreal-Colin P, et al. Intraoperative touch imprint cytology of sentinel lymph nodes in breast cancer:experience at a tertiary care center in Mexico[J]. Med Oncol.2010,27(2):233-236.
[11]Hamidian JA, Narayanan S, MacNeill F, et al. Testing the feasibility of intra-operative sentinel lymph node touch imprint cytology.[J]. Ann R Coll Surg Engl,2009,91(4):336-339.
[12]Contractor K, Gohel M, Al-Salami E, et al. Intra-operative imprint cytology for assessing the sentinel node in breast cancer:results of its routine use over 8 years.[J]. Eur J Surg Oncol,2009,35(1):16-20.
[13]Feng J, Bernacki EG. Intraoperative cytologic evaluation of sentinel lymph nodes in patients with breast carcinoma by scrape preparation[J]. Diagn Cytopathol, 2008,36(11):790-793.
[14]Creager AJ, Geisinger KR, Shiver SA, et al. Intraoperative evaluation of sentinel lymph nodes for metastatic breast carcinoma by imprint cytology [J]. Mod Pathol, 2002,15(11):1140-1147.
[15]Cox C, Centeno B, Dickson D, et al. Accuracy of intraoperative imprint cytology for sentinel lymph node evaluation in the treatment of breast carcinoma[J]. Cancer,2005,105(1):13-20.
[16]Motomura K, Nagumo S, Komoike Y, et al. Intraoperative imprint cytology for the diagnosis of sentinel node metastases in breast cancer[J]. Breast Cancer, 2007,14(4):350-353.
[17]Langer I, Guller U, Berclaz G, et al. Accuracy of frozen section of sentinel lymph nodes:a prospective analysis of 659 breast cancer patients of the Swiss multicenter study [J]. Breast Cancer Res Treat,2009,113(1):129-136.
[18]Creager AJ, Geisinger KR. Intraoperative Evaluation of Sentinel Lymph Nodes for Breast Carcinoma:Current Methodologies[J]. Adv Anat Pathol, 2002,9(4):233-243.
[19]Noriaki W, Shigeru I, Takahiro H, et al. Evaluation of Intraoperative Frozen Section Diagnosis of Sentinel Lymph Nodes in Breast Cancer[J]. Jpn J Clin Oncol,2004,34(3):113-117.
[20]van de Vrande S, Meijer J, Rijnders A, et al. The value of intraoperative frozen section examination of sentinel lymph nodes in breast cancer[J]. Eur J Surg Oncol, 2009,35(3):276-280.
[21]Chao C. The use of frozen section and immunohistchemistry for sentinel lymph node biopsy in breast cancer [J]. Am Surg,2004,70(5):414-419.
[22]Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol,2005,23(30):7703-7720.
[23]Cserni G, Amendoeira I, Apostolikas N, et al. Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology [J]. J Clin Pathol,2004,57(7):695-701.
[24]Goyal A, Mansel RE. Recent advances in sentinel lymph node biopsy for breast cancer.[J]. Curr Opin Oncol,2008,20(6):621-626.
[25]Giobuin SM, Kavanagh DO, Myers E, et al. The significance of immunohistochemistry positivity in sentinel nodes which are negative on haematoxylin and eosin in breast cancer [J]. Eur J Surg Oncol, 2009,35(12):1257-1260.
[26]Cserni G, Bianchi S, Vezzosi V. The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma[J]. J Clin Pathol.,2006,59(5):518-522.
[27]Cserni G, Gregori D, Merletti F, et al. Meta-analysis of non-sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer [J]. British Journal of Surgery,2004,91:1245-1252.
[28]Mullenix PS, Brown TA, Meyers MO, et al. The association of cytokeratin-only-positive sentinel lymph nodes and subsequent metastases in breast cancer [J]. Am J Surg,2005,189(5):606-609.
[29]Young JC, Hae RY, Ki EY, et al. Intraoperative Examination of Sentinel Lymph Nodes by Ultrarapid Immunohistochemistry in Breast Cancer [J].Jpn J Clin Oncol,2006,36(8):489-493.
[30]Holm M, Paaschburg B, Balslev E, et al. Intraoperative immunohistochemistry staining of sentinel nodes in breast cancer:clinical and economical implications[J]. Breast,2008,17(4):372-375.
[31]Jylling AM, Lindebjerg J, Nielsen L, et al. Immunohistochemistry on Frozen Section of Sentinel Lymph Nodes in Breast Cancer With Improved Morphology and Blocking of Endogenous Peroxidase[J]. Appl Immunohistochem Mol Morphol,2008,16:482-484.
[32]Turner RR, Ollila DW, Stem S, et al. Optimal histopathologic examination of the sentinel lymph node for breast carcinoma staging[J]. Am J Surg Pathol, 1999,23:263.
[33]Nahrig J, Richter T, Kowolik J, et al. Comparison of different histopathological methods for the examination of sentinel lymph nodes in breast cancer[J]. Anticancer Res,2000,20:2209-2212.
[34]Ollila DB, Stitzenberg K. Breast cancer sentinel node metastases:histopathologic detection and clinical significance[J]. Cancer Control,2001,8(5):407-414.
[35]Viale G, Maiorano E, Mazzarol G, et al. Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma[J]. Cancer,2001,92:1378-1384.
[36]Kanngurn S, Chewatanakornkul S, Premprapha T, et al. Comparability of different pathologic protocols in sentinel lymph node evaluation:an analysis of two step-sectioning methods for the same patients with breast cancer[J]. Arch Pathol Lab Med.,2009,133(9):1437-1440.
[37]van Diest PJ, Peterse HL, Borgstein PJ, et al. Pathological investigation of sentinel lymph nodes[J], Eur J Nucl Med,1999,26(Suppl):S43-S49.
[38]Martin M, Veys I, Majjaj S, et al. Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes [J]. Eur J Surg Oncol,2009,35(4):387-392.
[39]Blumencranz P, Whitworth PW, Deck K, et al. Sentinel node staging for breast cancer:intraoperative molecular pathology overcomes conventional histologic sampling errors[J]. Am J Surg,2007,194:426-432.
[40]Julian TB, Blumencranz P, Deck K, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer.[J]. J Clin Oncol,2008,26(20):3338-3345.
[41]Viale G, Dell'Orto P, Biasi MO, et al. comparative evaluation of an Extensive Histopathologic Examination and a Real-Time Reverse-Transcription-Polymerase chain Reaction Assay for Mammaglobin and Cytokeratin 19 on Axillary Sentinel Lymph Nodes of Breast Carcinoma Patients[J]. Ann Surg,2008,247(1):136-142.
[42]Lefferts JA, Bartels CL, Tsongalis GJ. Molecular oncology:current trends in diagnostics[J]. Future Oncol,2008,4(1):61-70.
[43]Veys I, Durbecq V, Majjaj S, et al. Eighteen months clinical experience with the GeneSearch breast lymph node assay [J]. Am J Surg,2009,198(2):203-209.
[44]Tamaki Y, Akiyama F, Iwase T, et al. Molecular detection of lymph node metastases in breast cancer patients:results of a multicenter trial using the one-step nucleic acid amplification assay [J]. Clin Cancer Res, 2009,15(8):2879-2884.
[45]Schem C, Maass N, Bauerschlag DO, et al. One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group [J]. Virchows Arch, 2009,454(2):203-210.
[46]Tsujimoto M, Nakabayashi K, Yoshidome K, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients[J]. Clin Cancer Res,2007,13(16):4807-4816.
[47]Le Frere-Belda MA, Bats AS, Gillaizeau F, et al. Diagnostic performance of one-step nucleic acid amplification for intraoperative sentinel node metastasis detection in breast cancer patients[J]. Int J Cancer,2012,15;130(10):2377-2386.
[48]Osako T, Iwase T, Kimura K, et al. Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer:A comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology[J]. Cancer,2011,117(19):4365-4374.
[49]Snook KL, Layer GT, Jackson PA, et al. Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma[J]. Br J Surg, 2011,98(4):527-535.
[50]Feldman S, Krishnamurthy S, Gillanders W, et al. A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes[J]. Cancer,2011,117(12):2599-2607.
[51]Visser M, Jiwa M, Horstman A, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer[J]. Int J Cancer,2008,122(11):2562-2567.
[52]Bernet L, Cano R, Martinez M, et al. Diagnosis of the sentinel lymph node in breast cancer:a reproducible molecular method:a multicentric Spanish study[J]. Histopathology,2011,58(6):863-869.
[53]Reed J, Rosman M, Verbanac KM, et al. Prognostic Implications of Isolated Tumor Cells and Micrometastases in Sentinel Nodes of Patients with Invasive Breast Cancer:10-Year Analysis of Patients Enrolled in the Prospective East Carolina University/Anne Arundel Medical Center Sentinel Node Multicenter Study [J]. J Am Coll Surg,2009,208(3):334-340.
[54]Houvenaeghel G, Nos C, Mignotte H. Micrometastases in sentinel lymph node in a multicentric study:redictive factors of nonsentinel lymph node involvement[J]. J Clin Oncol,2006,24(12):1814-1822.
[55]Viale G, Maiorano E, Pruneri G. Predicting the risk for additional axillary metastases in patients with breast carcinoma and positive sentinel lymph node biopsy [J]. Ann Surg,2005,241(2):319-325.
[56]Rutgers EJ. Sentinel Node Biopsy:Interpretation and Management of Patients With Immunohistochemistry-Positive Sentinel Nodes and Those With Micrometastases[J]. J Clin Oncol,2008,26(5):698-702.
[57]Ludwig Breast Cancer Study Group. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. International (Ludwig) Breast Cancer Study Group[J]. Lancet,1990,335:1565-1568.
[58]Cox CE, Kiluk JV, Riker AL. Significance of sentinel node micrometastases in human breast cancer[J]. J Am Coll Surg,2008,206:261-268.
[59]Marinho VF, Zagury MS, Caldeira LG, et al. Relationship between histologic features of primary breast carcinomas and axillary lymph node micrometastases: Detection and prognostic significance[J]. Appl Immunohistochem Mol Morphol, 2006,14(4):426-431.
[60]Bulte CS, van der Heiden-van der Loo M, Hennipman A. Axillary recurrence rate after tumour negative and micrometastatic positive sentinel node procedures in breast cancer patients, a population based multicenter study [J]. Eur J Surg Oncol, 2009,35(l):25-31.
[61]Hansen NM, Grube B, Ye X, et al. Impact of micrometastases in the sentinel node of patients with invasive breast cancer[J]. J Clin Oncol,2009,27(28):4679-4684.
[62]Onishi T, Jinno H, Takahashi M, et al. Non-sentinel lymph node status and prognosis of breast cancer patients with micrometastatic sentinel lymph nodes[J]. Eur Surg Res,2010,45(3-4):344-349.
[63]Langer I, Marti WR, Guller U, et al. Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy[J]. Ann Surg, 2005,241(1):152-158.
[64]Wasif N, Ye X, Giuliano AE. Survey of ASCO members on management of sentinel node micrometastases in breast cancer:variation in treatment recommendations according to specialty [J]. Ann Surg Oncol, 2009,16(9):2442-2449.
[65]Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases:the American College of Surgeons Oncology Group Z0011 randomized trial [J]. Ann Surg,2010,252(3):426-432,432-433.
[66]Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis:a randomized clinical trial[J]. JAMA,2011,305(6):569-575.
[67]Olsen SB, Amr B, Omar A, et al. Are the Findings of ASOCOG Z0011 Applicable to District General Hospital Breast Unit-And How Should They Change Our Practice?:San Antonio Breast Cancer Symposium,San Antonio Texas USA, December 6-10,2011[C].Berlin:Springer,c2000.
[68]Schwartz GF, Solin LJ, Olivotto IA, et al. The consensus conference on the treatment of in situ ductal carcinoma of the breast, April 22-25,1999[J]. Breast, 2000,9(4):177-186.
[69]Cox CE, Nguyen K, Gray RJ, et al. Importance of lymphatic mapping in ductal carcinoma in situ (DCIS):why map DCIS?[J]. Am Surg,2001,67(6):513-519, 519-521.
[70]Cserni G. Sentinel lymph node biopsy as a tool for the staging of ductal carcinoma in situ in patients with breast carcinoma[J]. Surg Today, 2002,32(2):99-103.
[71]Dominguez FJ, Golshan M, Black DM, et al. Sentinel node biopsy is important in mastectomy for ductal carcinoma in situ[J]. Ann Surg Oncol, 2008,15(1):268-273.
[72]Farkas EA, Stolier AJ, Teng SC, et al. An argument against routine sentinel node mapping for DCIS[J]. Am Surg,2004,70:13-17.
[73]Intra M, Veronesi P, Mazzarol G, et al. Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast[J]. Arch Surg, 2003,138(3):309-313.
[74]Katz A, Gage I, Evans S, et al. Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer[J]. Am J Surg, 2006,191(6):761-766.
[75]Kelly TA, Kim JA, Patrick R, et al. Axillary lymph node metastases in patients with a final diagnosis of ductal carcinoma in situ[J]. Am J Surg, 2003,186(4):368-370.
[76]Mabry H, Giuliano AE, Silverstein MJ. What is the value of axillary dissection or sentinel node biopsy in patients with ductal carcinoma in situ?[J]. Am J Surg, 2006,192(4):455-457.
[77]Sakr R, Barranger E, Antoine M, et al. Ductal carcinoma in situ:value of sentinel lymph node biopsy[J]. J Surg Oncol,2006,94(5):426-430.
[78]Veronesi P, Intra M, Vento AR, et al. Sentinel lymph node biopsy for localised ductal carcinoma in situ?[J]. Breast,2005,14(6):520-522.
[79]Zavagno G, Carcoforo P, Marconato R, et al. Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast[J]. BMC Cancer,2005,5:28.
[80]Sakr R, Antoine M, Barranger E, et al. Value of sentinel lymph node biopsy in breast ductal carcinoma in situ upstaged to invasive carcinoma[J]. Breast J, 2008,14(1):55-60.
[81]van la Parra RF, Ernst MF, Barneveld PC, et al. The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast[J]. Eur J Surg Oncol,2008,34(6):631-635.
[82]Klauber-DeMore N, Tan LK, Liberman L, et al. Sentinel lymph node biopsy:is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?[J]. Ann Surg Oncol,2000,7(9):636-642.
[83]D'Eredita G, Giardina C, Napoli A, et al. Sentinel lymph node biopsy in patients with pure and high-risk ductal carcinoma in situ of the breast.[J]. Tumori, 2009,95(6):706-711.
[84]DeSantis C, Siegel R, Bandi P, et al. Breast cancer statistics,2011[J]. CA Cancer J Clin,2011,61 (6):409-418.
[85]van de Vijver MJ, He YD, Van'T VL, et al. A gene-expression signature as a predictor of survival in breast cancer[J]. N Engl J Med,2002,347(25):1999-2009.
[86]Chelouche-Lev D, Kluger HM, Berger AJ, et al. alphaB-crystallin as a marker of lymph node involvement in breast carcinoma. [J]. Cancer, 2004,100(12):2543-2548.
[87]房爱菊,孟斌,刘文君,等α-B crystallin在乳腺浸润性导管癌中的表达及意义[J].山东大学学报(医学版),2008,46(3)：280-283.
[88]Moyano JV, Evans JR, Chen F, et al. AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer.[J]. J Clin Invest, 2006,116(1):261-270.
[89]Magnaldo T, Bernerd F, Darmon M. Galectin-7, a human 14-kDa S-lectin, specifically expressed in keratinocytes and sensitive to retinoic acid[J]. Dev Biol,1995,168(2):259-271.
[90]Timmons PM, Colnot C, Cail I, et al. Expression of galectin-7 during epithelial development coincides with the onset of stratification[J]. Int J Dev Biol, 1999,43(3):229-235.
[91]Kuwabara I, Kuwabara Y, Yang RY, et al. Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release[J]. J Biol Chem,2002,277(5):3487-3497.
[92]Bernerd F, Sarasin A, Magnaldo T. Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes[J]. Proc Natl Acad SciUS A,1999,96(20):11329-11334.
[93]Ueda S, Kuwabara I, Liu FT. Suppression of tumor growth by galectin-7 gene transfer[J]. Cancer Res,2004,64(16):5672-5676.
[94]Kopitz J, Andre S, von Reitzenstein C, et al. Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells[J]. Oncogene,2003,22(40):6277-6288.
[95]Lu J, Pei H, Kaeck M, et al. Gene expression changes associated with chemically induced rat mammary carcinogenesis[J]. Mol Carcinog,1997,20(2):204-215.
[96]Rorive S, Eddafali B, Fernandez S, et al. Changes in galectin-7 and cytokeratin-19 expression during the progression of malignancy in thyroid tumors: diagnostic and biological implications[J]. Mod Pathol,2002,15(12):1294-1301.
[97]Chen J, He QY, Yuen AP, et al. Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis[J]. Proteomics, 2004,4(8):2465-2475.
[98]Zhu X, Ding M, Yu ML, et al. Identification of galectin-7 as a potential biomarker for esophageal squamous cell carcinoma by proteomic analysis[J]. BMC Cancer,2010,10:290.
[99]Demers M, Rose AA, Grosset AA, et al. Overexpression of galectin-7, a myoepithelial cell marker, enhances spontaneous metastasis of breast cancer cells[J]. Am J Pathol,2010,176(6):3023-3031.