甲状腺癌的超声显像与骨桥蛋白表达及微血管密度测定的相关研究
|
摘要
第一部分彩色多普勒超声诊断甲状腺癌的多因素分析
背景
甲状腺癌是头颈部比较常见的恶性肿瘤,近年来发病率有上升趋势,早期甲状腺癌经手术切除后,几乎可以根治,而晚期甲状腺癌则会发生淋巴结、肺、骨等远处转移,早期诊断、早期治疗至关重要。目前,临床上对甲状腺癌的诊断主要依靠触诊及影像学检查(高频超声、核素、CT、MRI)及免疫学测定等,其中,彩色多普勒超声是目前甲状腺及颈部疾病最重要的检查手段,随着多种超声显像技术的不断改进和应用,超声能够观察到2～3mm的微小病灶,能够较清晰地显示病灶内部结构、有无包膜和微钙化等细微结构的改变以及病灶血流分布和血流频谱的变化,为进一步提高甲状腺疾病的诊断率提供了有利条件。然而,由于甲状腺结节病理类型繁多,生物学特性差异大,且具有多发性及多源性的特点,使得超声对部分不典型结节的诊断存在困难,在超声检查中还存在一定比例的漏诊和误诊,对于部分良恶性结节的鉴别尚有争议。
目的
通过观察145例经手术和病理证实的甲状腺结节的彩色多普勒超声表现,将声像图表现与病理结果结合进行单因素和Logistic多因素分析,以获得超声诊断甲状腺癌的最相关的声像图指标,为方便、快捷地鉴别甲状腺良、恶性结节提供理论依据。
方法
选择2006年2月至2008年8月因甲状腺结节在我院普外科收治的患者145例,所有患者术前行彩色多普勒超声检查,观察并记录病灶的二维及彩色多普勒图像表现,包括病灶数目、大小、边界、内部回声、砂粒样强回声、声晕、后方衰减、血流分级及血流阻力指数、颈部肿大淋巴结等。术后与病理对照。将甲状腺良、恶性结节超声表现结合病理结果进行单因素和Logistic多因素回归分析,筛选甲状腺癌相关声像图指标。
结果
145例甲状腺结节包括乳头状癌48例,滤泡样癌6例,髓样癌2例,转移癌1例;结节性甲状腺肿69例,甲状腺腺瘤19例。
57例甲状腺癌中,边界模糊者39例(68.4%);低回声46例(80.7%),有砂粒样强回声35例(61.4%),有后方衰减21例(36.8%),血流阻力指数＞0.7者19例(33.3%),有淋巴结转移23例(40.4%)。颈部肿大淋巴结位于中颈部者占76%(19/25)。转移淋巴结表现为增大、变圆,皮质增厚,髓质偏心或消失,内部回声增强,不均匀,可见砂粒样强回声,可呈不同程度囊性改变,实性淋巴结内血流增多、紊乱。88例甲状腺良性结节中,边界模糊者8例(9.1%),低回声26例(29.5%),有砂粒样强回声4例(4.5%),有后方衰减6例(6.8%),血流阻力指数＞0.7者5例(5.7%)。
经单因素分析,对诊断甲状腺癌有意义的声像图表现有单发病灶、边界模糊、低回声、砂粒样强回声、后方衰减及高血流阻力。
经Logistic多因素回归分析,甲状腺癌相关声像图特征为:砂粒样强回声、低回声、边界模糊及单发病灶。
结论
1.经Logistic多因素相关回归分析显示,单发病灶、砂粒样强回声(微钙化)、低回声、边界模糊,为诊断甲状腺癌的主要依据。
2.甲状腺癌的淋巴结转移常为多分区转移,Ⅲ区(中颈部)为最常见的转移部位;主要声像图特点有:淋巴结增大、变圆,皮髓质分界不清,淋巴门结构破坏或消失;淋巴结内部回声偏强,有时可出现较多细小点状钙化;部分淋巴结内部出现囊性改变。
3.彩色多普勒超声对甲状腺良恶性结节的鉴别诊断具有重要意义,能为临床诊断及治疗提供准确信息。
第二部分乳头状甲状腺癌的超声表现与骨桥蛋白表达的关系研究
背景
甲状腺癌是头颈部最常见的恶性肿瘤之一,近年来发病率有增长趋势,乳头状甲状腺癌占所有甲状腺恶性肿瘤的75%以上,其发病机理及生物学过程至今不明。骨桥蛋白(osteopontin,OPN)是一种含有特异RGD序列的分泌型磷酸化糖蛋白,具有促进细胞趋化、黏附和迁移的功能,近年来,OPN与肿瘤的发生发展,特别是它与肿瘤转移的关系日益引起人们的关注。目前,已有文献报道OPN在乳腺癌、结肠癌、胃癌、肝癌、卵巢癌等多种恶性肿瘤中呈高表达,在头颈部癌(包括甲状腺癌)的报道较少见。本文通过研究乳头状甲状腺癌组织中的OPN表达情况及探讨其与超声表现之间的关系,旨在研究乳头状甲状腺癌的分子生物学机制,以期为乳头状甲状腺癌的生物学行为和预后进行评估。
目的
分别从mRNA和蛋白质水平检测骨桥蛋白(OPN)在乳头状甲状腺癌中的表达,探讨OPN的表达与乳头状甲状腺癌超声表现特征之间的关系。
方法
1.彩色多普勒超声检查
对48例乳头状甲状腺癌患者术前行甲状腺彩色多普勒超声检查,分析其声像图特征。
2.实时荧光定量PCR(FQ-PCR)法检测OPNmRNA的表达
收集48例乳头状甲状腺癌及对照组(30例甲状腺良性病变及20例正常甲状腺组织)的术后标本,分别从标本组织中提取总RNA,经逆转录反应得到cDNA,以GAPDH基因作为参照,通过实时定量PCR技术检测OPNmRNA的表达。
分析OPNmRNA的表达与各项超声表现特征之间的关系。
3.免疫组织化学检测
取组织切片,用免疫组织化学法行OPN的组织学检测,观察乳头状甲状腺癌及对照组的OPN蛋白表达情况。结果
1.乳头状甲状腺癌中OPNmRNA的表达水平为56.82±49.16,高于甲状腺良性病变(19.72±28.56)及正常甲状腺组织(13.76±20.65)(P＜0.05)。
2.免疫组织化学结果表明,OPN主要定位于癌细胞的细胞质,乳头状甲状腺癌中OPN蛋白阳性表达高于甲状腺良性病变及正常甲状腺组织(P＜0.05)。
3.本组病例超声显示微钙化的乳头状甲状腺癌组织中OPNmRNA的表达水平(68.89±67.96)明显高于超声未显示微钙化者(20.62±15.90),伴淋巴结转移的癌组织OPNmRNA的表达(81.26±67.08)高于无淋巴结转移者(38.83±34.69)(P＜0.05)。超声显示的肿块大小、肿块边界及血流分级与OPN表达无明显相关。
结论
1.OPN在乳头状甲状腺癌组织中高表达,OPN在乳头状甲状腺癌的发生、发展中起到一定作用。
2.乳头状甲状腺癌OPNmPNA的表达量与超声显示的微钙化及淋巴结转移存在相关性,OPN可能参与了微钙化的形成,超声表现在一定程度上反映了肿瘤组织中OPN的表达水平,对评估乳头状甲状腺癌的生物学行为和预后具有一定价值。
第三部分乳头状甲状腺癌的超声表现与微血管密度测定的相关研究
背景
肿瘤新生血管形成在其生长、侵袭转移中起着重要作用,研究肿瘤新生血管一直是目前肿瘤研究的热点。测量微血管密度(MVD)是目前常用的评价肿瘤血管生成情况的方法,MVD能较为精确地反映肿瘤内的血管状态,已被公认为是预测肿瘤预后的一个独立指标。目前认为多数实体肿瘤MVD明显增高,并与其侵袭性有关。CD34是一种新型的微血管标记物,其显示血管内皮细胞时,更具敏感性和特异性,易于观察,用抗CD34抗体作微血管染色较其它标记物能提供更多有用而可靠的信息。
目前随着彩色多普勒超声的广泛使用,超声检查已成为临床诊断甲状腺疾病的主要检查手段之一,对良恶性结节的鉴别诊断已积累了一定的经验,但在部分结节的鉴别诊断方面仍有争议。近年来微血管密度测定技术的发展为甲状腺结节性疾病的诊断提供了一个新的方向,MVD可精确标识肿瘤组织内微血管,而超声血流显像则是对肿瘤内血管分布的宏观测估,本研究拟探讨二者的内在联系,以为临床提供更多诊断及评估愈后的信息。
目的
通过对48例乳头状甲状腺癌及对照组的彩色多普勒超声检查、微血管密度测定,并与病理结果对照,分析声像图表现与微血管密度之间的关系,评价彩色多普勒超声、微血管密度测定在乳头状甲状腺癌中的诊断价值。
方法
1.彩色多普勒超声检查
采用ATL HDI-5000及GE LOGIQ 9彩色超声诊断仪,观查并记录48例乳头状甲状腺癌的声像图表现。二维超声观察甲状腺结节的部位、大小、数目、边界、内部回声及钙化情况、颈部有无肿大淋巴结等。用彩色多普勒血流显像(CDFI)及彩色多普勒能量显像(PDI)技术检测每个结节内部血流情况,将结节内部血流丰富程度按Alder半定量法分为0～Ⅲ级。
2.微血管密度测定
用抗CD34单克隆抗体作免疫组化染色,检测48例乳头状甲状腺癌、30例甲状腺良性病变及20例正常甲状腺组织中的微血管密度,在200倍视野下(0.739mm~2)由两名计数者以双盲法对每一例标本作微血管计数,取二者的均数为该例的MVD值。
结果
1.乳头状甲状腺癌的超声表现
本组乳头状甲状腺癌最常见的声像图表现为不规则形低回声结节,边界模糊和结节内回声不均质及簇状“砂粒样”强回声。常伴有淋巴结转移。结节内部血流分级:0级9例,Ⅰ级13例,Ⅱ级16例,Ⅲ级10例。
2.甲状腺良恶性结节微血管密度值
乳头状甲状腺癌组织微血管密度值(126.8±42.1)高于甲状腺良性病变(90.2±38.5)和正常甲状腺组织(73.7±27.6)(P＜0.05),甲状腺良性病变与正常甲状腺组织间差异无统计学意义(P＞0.05)。
3.乳头状甲状腺癌超声血流分级与微血管密度
不同血流分级微血管密度均值分别为:91.3±35.4(0级),105.5±30.8(Ⅰ级),137.5±43.0(Ⅱ级),169.3±37.2(Ⅲ级)。经方差分析,各级间数值差异有统计学意义(P＜0.05),Ⅱ级显著高于0级和Ⅰ级,Ⅲ级显著高于Ⅱ级。随血流分级的增高,微血管密度显著增高。
4.乳头状甲状腺癌声像图特征与微血管密度的相关性
体积较大的结节(≥2cm)22例,微血管密度值为140.1±37.8,体积较小的结节(＜2cm)26例,微血管密度值为115.5±43.3,两组间差异有统计学意义(P＜0.05),表明体积较大结节的微血管密度高于较小结节。淋巴结转移阳性组微血管密度值为145.3±44.5,淋巴结转移阴性组为114.7±36.7,经t检验,两组间差别有统计学意义(P＜0.05),表明乳头状甲状腺癌淋巴结转移阳性组微血管密度值高于阴性组。结节边界和砂粒样钙化与微血管密度均无明显相关(P＞0.05)。
结论
1.乳头状甲状腺癌的微血管密度高于甲状腺良性病变及正常甲状腺组织。
2.乳头状甲状腺癌的二维声像图特征中,结节大小及淋巴结转移与微血管密度相关;彩色多普勒超声显示的血流分级能反映微血管密度。
3.彩色多普勒超声与微血管密度结合使用,将能更准确地反映肿瘤内的血管生成情况,能为乳头状甲状腺癌的临床诊断及预后评估提供更多信息。
Background
Thyroid cancer is common head and neck malignancies, in recent years, the disease incidence rate had the trend of escalation, the early-time thyroid cancer excised after the surgery, nearly may permanently cure, but the later-period thyroid cancer will have distant place shifts , such as lymph nodes, lungs, bone and other distant metastasis, early diagnosis, early treatment is essential. At present, the clinical diagnosis of thyroid cancer mainly depends on palpation and imaging (high-frequency ultrasound, radionuclide, CT, MRI) and immunoassay, etc, color Doppler ultrasound is currently the most important means of inspection for the thyroid and neck disease, with the development of ultrasound imaging and the application of new technologies, ultrasound can observe the minimal disease of 2-3mm ,and more clearly show the internal structure of nodules, with or without capsule and small structures such as micro-calcification changes, as well as color Doppler signals and Doppler changes in the spectrum, have provided favorable conditions to improve the diagnostic rate of thyroid disease. However, due to different types of pathological thyroid nodules, large differences in biological characteristics, and with multiple and multi-derived characteristics, ultrasonic performance of some nodules is not typical, there are difficulties in diagnosis, and there is a certain proportion of the missed diagnosis and misdiagnosis in the ultrasound examination, differential diagnosis of some benign and malignant nodules still controversial.
Objective
By observing the color Doppler ultrasonography performance of 145 cases of thyroid nodules confirmed by surgery and pathology , carried on the single factor and the multi-factor analysis, to obtain the most relevant ultrasonographic features for the diagnosis of thyroid cancer ,to provide a theoretical basis for identifying benign and malignant thyroid nodules easily.
Methods
Selected 145 cases of thyroid nodules admitting to our hospital general surgical department from June 2006 to August 2008. all patients were preoperatively with color Doppler ultrasonography, careful observation and recording of two-dimensional and color Doppler ultrasonic performance of lesions was made, including lesion number, size, border, internal echo, sand-like strong echoes, halo sound, rear attenuation, flow classification , flow resistance index,and neck lymph node swelling. After operation and pathology comparison, carried on the single factor and the Logistic multi-factor regression analysis, screened the thyroid cancer related ultrasonic characteristics.
Results
145 cases of thyroid nodules, including 48 cases of papillary carcinoma, 6 cases of follicular carcinoma, 2 cases of medullary carcinoma, 1 cases of metastatic carcinoma; 69 cases of nodular goiter, 19 cases of thyroid adenoma.
88 cases of benign thyroid nodules, 8 cases (9.1%)with fuzzy borders, low-echo 26cases (29.5%), 4 cases with sand-like strong echo (4.5%), 6 cases with rear attenuation (6.8%),5 cases with blood flow RI> 0.7 (5.7%); 57 cases of thyroid cancer , with fuzzy boundaries 39(68.4%); hypoechoic cases 46(80.7%), with sand-like strong echo 35cases (61.4%),21 cases with rear attenuation (36.8%),19cases with flow RI> 0.7 (33.3% ).23 cases with lymph node metastasis (40.4%). Swollen lymph nodes in the middle neck were 76% (19/25). Metastatic lymph nodes showed increasing and round, cortical thickening and medullary eccentric or disappear, internal echogenic heterogeneous, sand-like strong echoes, varying degrees of cystic change, blood flow increasing and disorder.
By single factor analysis, to diagnosis the thyroid cancer meaningful ultrasonic characteristics including single lesion. fuzzy border, low-echo, sand-like strong echoes, rear attenuation, high blood flow resistance and neck lymph node swelling.
By Logistic regression analysis, thyroid cancer associated sonographic characteristics including: single lesion ,sand-like strong echoes, hypoechoic, and boundary ambiguity.
Conclusions
1. Multi-factor Logistic regression analysis showed that, the related factors for diagnosis of thyroid cancer includes: single lesion ,sand-like strong echoes (microcalcification), low echo, and boundary ambiguity.
2. Lymph node metastasis of thyroid cancer often was multi-division transfer, III District (in the middle neck) as the most common metastatic sites; the main ultrasonic features included: lymph nodes increased, round, corticomedullary demarcation, lymph gate structure destroyed or disappeared; lymph internal echo heterogeneous, and sometimes may appear sand-like strong echoes; some cystic changes occur within lymph nodes.
3. Color Doppler ultrasound is of great significance in the differential diagnosis of benign and malignant thyroid nodules , can provide accurate information for the clinical diagnosis and treatment.
PART TWO Expression of osteopontin in thyroid papillary carcinoma and its relationship with ultrasonographic features.
Background
Thyroid cancer is common head and neck malignancies, in recent years, the disease incidence rate had the trend of escalation, of all thyroid malignancies papillary thyroid carcinoma accounts for more than 75 percent, and its pathogenesis and biological processes are not yet completely clear. Osteopontin (OPN) is a calcium-binding secreted phosphorylated glycoprotein containing specific RGD- sequence, with the promotion of cell chemotaxis, adhesion and migration functions. At present, OPN has been reported in the breast, colon, stomach, liver, ovarian cancer and other malignant tumors with high expression,but in head and neck cancer (including thyroid cancer) reported rare. In this paper, by studying expression of OPN in papillary thyroid carcinoma and investigating the relationship between expression of OPN and ultrasonic performance of papillary thyroid carcinoma, to study the molecular mechanisms of papillary thyroid cancer ,and to evaluate the biological behavior and prognosis of the tumor.
Objective
To investigate the expression of osteopontin(OPN) in human thyroid papillary carcinoma and its relationship with ultrasonographic features.
Methods
Ultrasonographic scanning was performed in 48 patients with thyroid papillary carcinoma before operation, ultrasonographic features were analyzed. The 48 specimens were collected, the expressions of OPN mRNA and protein were analyzed by using FQ - PCR and immunohistochemical staining respectively. 30 samples of thyroid benign lesions and 20 samples of normal thyroid tissues were selected as control group. Results of OPN expressions were compared with ultrasonographic features.
Results
The expression levels of OPN mRNA and protein in thyroid papillary carcinoma were higher than those of control. Expression of OPN was significant related with the presence of microcalcification in ultrasonography,the expression of OPN in microcalcification group was higher than that in non-microcalcification group. The expression of OPN in the group with lymph nodes metastasis was higher than that in the group without lymph nodes metastasis. No significant relevance was found between the expression of OPN and other ultrasonographic features(include tumor size, margin and blood flow).
Conclusions
The expression levels of OPN in thyroid papillary carcinoma were higher than that in benign lesions and normal thyroid tissues. OPN may play an important role in the development of thyroid papillary carcinoma ; The expression levels of OPN mRNA was related with the presence of microcalcification and lymph nodes metastasis in ultrasonography. OPN may take part in the formation of the microcalcification, the ultrasonographic features can reflect the expression of OPN, so the biological behavior and prognosis of thyroid papillary carcinoma can be assessed by ultrasonographic features to some extent.
PART THREE Microvessel Density Determination in Thyroid Papillary Carcinoma and its Relationship with Ultrasonographic Features.
Background
Tumor angiogenesis plays an important role in its growth, invasion and metastasis, studying tumor angiogenesis in cancer research has been hot, measuring microvessel density (MVD) is now commonly used in evaluation of tumor angiogenesis, MVD can precisely reflect the angiogenesis in the tumor, has been regarded as an independent indicator for prediction of tumor prognosis. At present,in the majority of solid tumors , MVD was significantly increased and related to their invasiveness. CD34 is a new type of microvascular markers, which shows the vascular endothelial cells, the more sensitivity and specificity, ease of observation, with anti-CD34 antibody for microvessel staining can provide more useful and reliable information than the other markers.
At present, with the extensive use of ultrasonography ,color Doppler ultrasound has become one of the main inspection means for clinical diagnosis of thyroid disease, on the differential diagnosis of benign and malignant nodules has accumulated certain experience, but in some aspects of differential diagnosis of nodules is still controversial. In recent years , determination of MVD provides a new direction for the development of technology in thyroid nodular disease diagnosis, MVD accurately identifies tumor microvessel, and ultrasonic blood flow classification is the distribution of tumor blood vessels within the macro-test assessment, This study was to investigate the intrinsic link between the two ,and to provide more useful information for clinical diagnosis and assessment.
Objective
Through the observation of two-dimensional and color Doppler ultrasonography of 48 cases of papillary thyroid carcinoma and the control group, determination of MVD, compared with pathological results, evaluated color Doppler ultrasound and determination of MVD in the diagnosis of papillary thyroid carcinoma.
Methods
Color Doppler ultrasonic examination
Using ATL HDI-5000 and GE LOGIQ 9 color ultrasound diagnostic apparatus , observed and recorded the ultrasonography of 48 cases of papillary thyroid carcinoma. Two-dimensional ultrasonic observation of thyroid nodules included location, size, number, boundaries (fuzzy or clear), internal echo ,calcification (with particular attention to the existence of microcalcifications), neck lymph node swelling, and so on. Using color Doppler flow imaging (CDFI) and power Doppler imaging(PDI) to detect blood flow in each nodule, the nodule internal flow was divided into 4 levels(0-III) according to the Alder semi-quantitative methods.
Determination of MVD
With anti-CD34 monoclonal antibodies for immunohistochemical staining to detect the MVD in 48 cases of papillary thyroid carcinoma, 30 cases of benign thyroid lesions and 20 cases of normal thyroid tissue, made the capillaries counting in 200 time of fields (0.739mm~2) by two counters for each specimen for microvessel count using double-blind method, took the two's mean value for one specimen.
Results
Ultrasonic performance of Papillary thyroid carcinoma Papillary thyroid carcinoma in this group the most common sonographic performance showed irregular hypoechoic nodules, and nodules with fuzzy boundary , non-homogeneous and cluster "sand-like" strong echo, more than one strip flow points in the majority of nodules, often accompanied by lymph node metastasis. The flow in the nodules is divided into 4 levels according to the Alder semi-quantitative method, grade 0 9 cases , grade I 13 cases , grade II -III 26 cases.
MVD in benign and malignant thyroid nodules
MVD of papillary thyroid cancer tissue (126.8±42.1) is higher than that of benign thyroid lesions (95.2±38.5) and normal thyroid tissue (83.7±27.6)(p<0.05). The difference of MVD between benign thyroid lesions and normal thyroid tissue has no significances.
Papillary thyroid carcinoma power Doppler grading vs MVD
Mean MVD were: 97.3±35.4 (grade 0), 104.6±30.8 (grade I), 127.5±43.0 (grade II), 141.3±37.2 (grade III). By analysis of variance at all levels ,the numerical differences were significant (p<0.05),grade II was significantly higher than grade 0 and I, grade III were significantly higher than grade II, with the flow classification increased MVD was significantly higher.
Correlation between MVD and lymph node metastasis
MVD in lymph node metastasis positive group was 140.3±44.5, lymph node negative group was 116.0±36.7,by t-test, the difference between the two groups was statistically significant (p<0.05),showed that the MVD in papillary thyroid carcinoma lymph node metastasis positive group was higher than that of the negative group.
Correlation between papillary thyroid carcinoma sonographic features and MVD
MVD of 22 Larger nodules (≥2cm) was 139.4±37.8, 26 smaller nodules (<2cm) was 117.5±43.3, difference between the two groups was statistically significant (P<0.05), showed that larger nodules had higher MVD than smaller nodules. Nodular borders and gravel-like calcification were not significantly associated with MVD.
Conclusions
1. MVD of papillary thyroid carcinoma was higher than that of benign lesions and normal thyroid tissue.
2. Of ultrasonic features , the nodule size and lymph node metastasis were related to MVD significantly. The application of color Doppler Imaging accurately reflect the tumor microvessel situation.
3. Color Doppler ultrasound combined with the MVD determination will be able to more accurately reflect the tumor blood supply situation, and provide more information for clinical diagnosis and assessment.
背景
甲状腺癌是头颈部比较常见的恶性肿瘤,近年来发病率有上升趋势,早期甲状腺癌经手术切除后,几乎可以根治,而晚期甲状腺癌则会发生淋巴结、肺、骨等远处转移,早期诊断、早期治疗至关重要。目前,临床上对甲状腺癌的诊断主要依靠触诊及影像学检查(高频超声、核素、CT、MRI)及免疫学测定等,其中,彩色多普勒超声是目前甲状腺及颈部疾病最重要的检查手段,随着多种超声显像技术的不断改进和应用,超声能够观察到2～3mm的微小病灶,能够较清晰地显示病灶内部结构、有无包膜和微钙化等细微结构的改变以及病灶血流分布和血流频谱的变化,为进一步提高甲状腺疾病的诊断率提供了有利条件。然而,由于甲状腺结节病理类型繁多,生物学特性差异大,且具有多发性及多源性的特点,使得超声对部分不典型结节的诊断存在困难,在超声检查中还存在一定比例的漏诊和误诊,对于部分良恶性结节的鉴别尚有争议。
目的
通过观察145例经手术和病理证实的甲状腺结节的彩色多普勒超声表现,将声像图表现与病理结果结合进行单因素和Logistic多因素分析,以获得超声诊断甲状腺癌的最相关的声像图指标,为方便、快捷地鉴别甲状腺良、恶性结节提供理论依据。
方法
选择2006年2月至2008年8月因甲状腺结节在我院普外科收治的患者145例,所有患者术前行彩色多普勒超声检查,观察并记录病灶的二维及彩色多普勒图像表现,包括病灶数目、大小、边界、内部回声、砂粒样强回声、声晕、后方衰减、血流分级及血流阻力指数、颈部肿大淋巴结等。术后与病理对照。将甲状腺良、恶性结节超声表现结合病理结果进行单因素和Logistic多因素回归分析,筛选甲状腺癌相关声像图指标。
结果
145例甲状腺结节包括乳头状癌48例,滤泡样癌6例,髓样癌2例,转移癌1例;结节性甲状腺肿69例,甲状腺腺瘤19例。
57例甲状腺癌中,边界模糊者39例(68.4%);低回声46例(80.7%),有砂粒样强回声35例(61.4%),有后方衰减21例(36.8%),血流阻力指数＞0.7者19例(33.3%),有淋巴结转移23例(40.4%)。颈部肿大淋巴结位于中颈部者占76%(19/25)。转移淋巴结表现为增大、变圆,皮质增厚,髓质偏心或消失,内部回声增强,不均匀,可见砂粒样强回声,可呈不同程度囊性改变,实性淋巴结内血流增多、紊乱。88例甲状腺良性结节中,边界模糊者8例(9.1%),低回声26例(29.5%),有砂粒样强回声4例(4.5%),有后方衰减6例(6.8%),血流阻力指数＞0.7者5例(5.7%)。
经单因素分析,对诊断甲状腺癌有意义的声像图表现有单发病灶、边界模糊、低回声、砂粒样强回声、后方衰减及高血流阻力。
经Logistic多因素回归分析,甲状腺癌相关声像图特征为:砂粒样强回声、低回声、边界模糊及单发病灶。
结论
1.经Logistic多因素相关回归分析显示,单发病灶、砂粒样强回声(微钙化)、低回声、边界模糊,为诊断甲状腺癌的主要依据。
2.甲状腺癌的淋巴结转移常为多分区转移,Ⅲ区(中颈部)为最常见的转移部位;主要声像图特点有:淋巴结增大、变圆,皮髓质分界不清,淋巴门结构破坏或消失;淋巴结内部回声偏强,有时可出现较多细小点状钙化;部分淋巴结内部出现囊性改变。
3.彩色多普勒超声对甲状腺良恶性结节的鉴别诊断具有重要意义,能为临床诊断及治疗提供准确信息。
第二部分乳头状甲状腺癌的超声表现与骨桥蛋白表达的关系研究
背景
甲状腺癌是头颈部最常见的恶性肿瘤之一,近年来发病率有增长趋势,乳头状甲状腺癌占所有甲状腺恶性肿瘤的75%以上,其发病机理及生物学过程至今不明。骨桥蛋白(osteopontin,OPN)是一种含有特异RGD序列的分泌型磷酸化糖蛋白,具有促进细胞趋化、黏附和迁移的功能,近年来,OPN与肿瘤的发生发展,特别是它与肿瘤转移的关系日益引起人们的关注。目前,已有文献报道OPN在乳腺癌、结肠癌、胃癌、肝癌、卵巢癌等多种恶性肿瘤中呈高表达,在头颈部癌(包括甲状腺癌)的报道较少见。本文通过研究乳头状甲状腺癌组织中的OPN表达情况及探讨其与超声表现之间的关系,旨在研究乳头状甲状腺癌的分子生物学机制,以期为乳头状甲状腺癌的生物学行为和预后进行评估。
目的
分别从mRNA和蛋白质水平检测骨桥蛋白(OPN)在乳头状甲状腺癌中的表达,探讨OPN的表达与乳头状甲状腺癌超声表现特征之间的关系。
方法
1.彩色多普勒超声检查
对48例乳头状甲状腺癌患者术前行甲状腺彩色多普勒超声检查,分析其声像图特征。
2.实时荧光定量PCR(FQ-PCR)法检测OPNmRNA的表达
收集48例乳头状甲状腺癌及对照组(30例甲状腺良性病变及20例正常甲状腺组织)的术后标本,分别从标本组织中提取总RNA,经逆转录反应得到cDNA,以GAPDH基因作为参照,通过实时定量PCR技术检测OPNmRNA的表达。
分析OPNmRNA的表达与各项超声表现特征之间的关系。
3.免疫组织化学检测
取组织切片,用免疫组织化学法行OPN的组织学检测,观察乳头状甲状腺癌及对照组的OPN蛋白表达情况。结果
1.乳头状甲状腺癌中OPNmRNA的表达水平为56.82±49.16,高于甲状腺良性病变(19.72±28.56)及正常甲状腺组织(13.76±20.65)(P＜0.05)。
2.免疫组织化学结果表明,OPN主要定位于癌细胞的细胞质,乳头状甲状腺癌中OPN蛋白阳性表达高于甲状腺良性病变及正常甲状腺组织(P＜0.05)。
3.本组病例超声显示微钙化的乳头状甲状腺癌组织中OPNmRNA的表达水平(68.89±67.96)明显高于超声未显示微钙化者(20.62±15.90),伴淋巴结转移的癌组织OPNmRNA的表达(81.26±67.08)高于无淋巴结转移者(38.83±34.69)(P＜0.05)。超声显示的肿块大小、肿块边界及血流分级与OPN表达无明显相关。
结论
1.OPN在乳头状甲状腺癌组织中高表达,OPN在乳头状甲状腺癌的发生、发展中起到一定作用。
2.乳头状甲状腺癌OPNmPNA的表达量与超声显示的微钙化及淋巴结转移存在相关性,OPN可能参与了微钙化的形成,超声表现在一定程度上反映了肿瘤组织中OPN的表达水平,对评估乳头状甲状腺癌的生物学行为和预后具有一定价值。
第三部分乳头状甲状腺癌的超声表现与微血管密度测定的相关研究
背景
肿瘤新生血管形成在其生长、侵袭转移中起着重要作用,研究肿瘤新生血管一直是目前肿瘤研究的热点。测量微血管密度(MVD)是目前常用的评价肿瘤血管生成情况的方法,MVD能较为精确地反映肿瘤内的血管状态,已被公认为是预测肿瘤预后的一个独立指标。目前认为多数实体肿瘤MVD明显增高,并与其侵袭性有关。CD34是一种新型的微血管标记物,其显示血管内皮细胞时,更具敏感性和特异性,易于观察,用抗CD34抗体作微血管染色较其它标记物能提供更多有用而可靠的信息。
目前随着彩色多普勒超声的广泛使用,超声检查已成为临床诊断甲状腺疾病的主要检查手段之一,对良恶性结节的鉴别诊断已积累了一定的经验,但在部分结节的鉴别诊断方面仍有争议。近年来微血管密度测定技术的发展为甲状腺结节性疾病的诊断提供了一个新的方向,MVD可精确标识肿瘤组织内微血管,而超声血流显像则是对肿瘤内血管分布的宏观测估,本研究拟探讨二者的内在联系,以为临床提供更多诊断及评估愈后的信息。
目的
通过对48例乳头状甲状腺癌及对照组的彩色多普勒超声检查、微血管密度测定,并与病理结果对照,分析声像图表现与微血管密度之间的关系,评价彩色多普勒超声、微血管密度测定在乳头状甲状腺癌中的诊断价值。
方法
1.彩色多普勒超声检查
采用ATL HDI-5000及GE LOGIQ 9彩色超声诊断仪,观查并记录48例乳头状甲状腺癌的声像图表现。二维超声观察甲状腺结节的部位、大小、数目、边界、内部回声及钙化情况、颈部有无肿大淋巴结等。用彩色多普勒血流显像(CDFI)及彩色多普勒能量显像(PDI)技术检测每个结节内部血流情况,将结节内部血流丰富程度按Alder半定量法分为0～Ⅲ级。
2.微血管密度测定
用抗CD34单克隆抗体作免疫组化染色,检测48例乳头状甲状腺癌、30例甲状腺良性病变及20例正常甲状腺组织中的微血管密度,在200倍视野下(0.739mm~2)由两名计数者以双盲法对每一例标本作微血管计数,取二者的均数为该例的MVD值。
结果
1.乳头状甲状腺癌的超声表现
本组乳头状甲状腺癌最常见的声像图表现为不规则形低回声结节,边界模糊和结节内回声不均质及簇状“砂粒样”强回声。常伴有淋巴结转移。结节内部血流分级:0级9例,Ⅰ级13例,Ⅱ级16例,Ⅲ级10例。
2.甲状腺良恶性结节微血管密度值
乳头状甲状腺癌组织微血管密度值(126.8±42.1)高于甲状腺良性病变(90.2±38.5)和正常甲状腺组织(73.7±27.6)(P＜0.05),甲状腺良性病变与正常甲状腺组织间差异无统计学意义(P＞0.05)。
3.乳头状甲状腺癌超声血流分级与微血管密度
不同血流分级微血管密度均值分别为:91.3±35.4(0级),105.5±30.8(Ⅰ级),137.5±43.0(Ⅱ级),169.3±37.2(Ⅲ级)。经方差分析,各级间数值差异有统计学意义(P＜0.05),Ⅱ级显著高于0级和Ⅰ级,Ⅲ级显著高于Ⅱ级。随血流分级的增高,微血管密度显著增高。
4.乳头状甲状腺癌声像图特征与微血管密度的相关性
体积较大的结节(≥2cm)22例,微血管密度值为140.1±37.8,体积较小的结节(＜2cm)26例,微血管密度值为115.5±43.3,两组间差异有统计学意义(P＜0.05),表明体积较大结节的微血管密度高于较小结节。淋巴结转移阳性组微血管密度值为145.3±44.5,淋巴结转移阴性组为114.7±36.7,经t检验,两组间差别有统计学意义(P＜0.05),表明乳头状甲状腺癌淋巴结转移阳性组微血管密度值高于阴性组。结节边界和砂粒样钙化与微血管密度均无明显相关(P＞0.05)。
结论
1.乳头状甲状腺癌的微血管密度高于甲状腺良性病变及正常甲状腺组织。
2.乳头状甲状腺癌的二维声像图特征中,结节大小及淋巴结转移与微血管密度相关;彩色多普勒超声显示的血流分级能反映微血管密度。
3.彩色多普勒超声与微血管密度结合使用,将能更准确地反映肿瘤内的血管生成情况,能为乳头状甲状腺癌的临床诊断及预后评估提供更多信息。
Background
Thyroid cancer is common head and neck malignancies, in recent years, the disease incidence rate had the trend of escalation, the early-time thyroid cancer excised after the surgery, nearly may permanently cure, but the later-period thyroid cancer will have distant place shifts , such as lymph nodes, lungs, bone and other distant metastasis, early diagnosis, early treatment is essential. At present, the clinical diagnosis of thyroid cancer mainly depends on palpation and imaging (high-frequency ultrasound, radionuclide, CT, MRI) and immunoassay, etc, color Doppler ultrasound is currently the most important means of inspection for the thyroid and neck disease, with the development of ultrasound imaging and the application of new technologies, ultrasound can observe the minimal disease of 2-3mm ,and more clearly show the internal structure of nodules, with or without capsule and small structures such as micro-calcification changes, as well as color Doppler signals and Doppler changes in the spectrum, have provided favorable conditions to improve the diagnostic rate of thyroid disease. However, due to different types of pathological thyroid nodules, large differences in biological characteristics, and with multiple and multi-derived characteristics, ultrasonic performance of some nodules is not typical, there are difficulties in diagnosis, and there is a certain proportion of the missed diagnosis and misdiagnosis in the ultrasound examination, differential diagnosis of some benign and malignant nodules still controversial.
Objective
By observing the color Doppler ultrasonography performance of 145 cases of thyroid nodules confirmed by surgery and pathology , carried on the single factor and the multi-factor analysis, to obtain the most relevant ultrasonographic features for the diagnosis of thyroid cancer ,to provide a theoretical basis for identifying benign and malignant thyroid nodules easily.
Methods
Selected 145 cases of thyroid nodules admitting to our hospital general surgical department from June 2006 to August 2008. all patients were preoperatively with color Doppler ultrasonography, careful observation and recording of two-dimensional and color Doppler ultrasonic performance of lesions was made, including lesion number, size, border, internal echo, sand-like strong echoes, halo sound, rear attenuation, flow classification , flow resistance index,and neck lymph node swelling. After operation and pathology comparison, carried on the single factor and the Logistic multi-factor regression analysis, screened the thyroid cancer related ultrasonic characteristics.
Results
145 cases of thyroid nodules, including 48 cases of papillary carcinoma, 6 cases of follicular carcinoma, 2 cases of medullary carcinoma, 1 cases of metastatic carcinoma; 69 cases of nodular goiter, 19 cases of thyroid adenoma.
88 cases of benign thyroid nodules, 8 cases (9.1%)with fuzzy borders, low-echo 26cases (29.5%), 4 cases with sand-like strong echo (4.5%), 6 cases with rear attenuation (6.8%),5 cases with blood flow RI> 0.7 (5.7%); 57 cases of thyroid cancer , with fuzzy boundaries 39(68.4%); hypoechoic cases 46(80.7%), with sand-like strong echo 35cases (61.4%),21 cases with rear attenuation (36.8%),19cases with flow RI> 0.7 (33.3% ).23 cases with lymph node metastasis (40.4%). Swollen lymph nodes in the middle neck were 76% (19/25). Metastatic lymph nodes showed increasing and round, cortical thickening and medullary eccentric or disappear, internal echogenic heterogeneous, sand-like strong echoes, varying degrees of cystic change, blood flow increasing and disorder.
By single factor analysis, to diagnosis the thyroid cancer meaningful ultrasonic characteristics including single lesion. fuzzy border, low-echo, sand-like strong echoes, rear attenuation, high blood flow resistance and neck lymph node swelling.
By Logistic regression analysis, thyroid cancer associated sonographic characteristics including: single lesion ,sand-like strong echoes, hypoechoic, and boundary ambiguity.
Conclusions
1. Multi-factor Logistic regression analysis showed that, the related factors for diagnosis of thyroid cancer includes: single lesion ,sand-like strong echoes (microcalcification), low echo, and boundary ambiguity.
2. Lymph node metastasis of thyroid cancer often was multi-division transfer, III District (in the middle neck) as the most common metastatic sites; the main ultrasonic features included: lymph nodes increased, round, corticomedullary demarcation, lymph gate structure destroyed or disappeared; lymph internal echo heterogeneous, and sometimes may appear sand-like strong echoes; some cystic changes occur within lymph nodes.
3. Color Doppler ultrasound is of great significance in the differential diagnosis of benign and malignant thyroid nodules , can provide accurate information for the clinical diagnosis and treatment.
PART TWO Expression of osteopontin in thyroid papillary carcinoma and its relationship with ultrasonographic features.
Background
Thyroid cancer is common head and neck malignancies, in recent years, the disease incidence rate had the trend of escalation, of all thyroid malignancies papillary thyroid carcinoma accounts for more than 75 percent, and its pathogenesis and biological processes are not yet completely clear. Osteopontin (OPN) is a calcium-binding secreted phosphorylated glycoprotein containing specific RGD- sequence, with the promotion of cell chemotaxis, adhesion and migration functions. At present, OPN has been reported in the breast, colon, stomach, liver, ovarian cancer and other malignant tumors with high expression,but in head and neck cancer (including thyroid cancer) reported rare. In this paper, by studying expression of OPN in papillary thyroid carcinoma and investigating the relationship between expression of OPN and ultrasonic performance of papillary thyroid carcinoma, to study the molecular mechanisms of papillary thyroid cancer ,and to evaluate the biological behavior and prognosis of the tumor.
Objective
To investigate the expression of osteopontin(OPN) in human thyroid papillary carcinoma and its relationship with ultrasonographic features.
Methods
Ultrasonographic scanning was performed in 48 patients with thyroid papillary carcinoma before operation, ultrasonographic features were analyzed. The 48 specimens were collected, the expressions of OPN mRNA and protein were analyzed by using FQ - PCR and immunohistochemical staining respectively. 30 samples of thyroid benign lesions and 20 samples of normal thyroid tissues were selected as control group. Results of OPN expressions were compared with ultrasonographic features.
Results
The expression levels of OPN mRNA and protein in thyroid papillary carcinoma were higher than those of control. Expression of OPN was significant related with the presence of microcalcification in ultrasonography,the expression of OPN in microcalcification group was higher than that in non-microcalcification group. The expression of OPN in the group with lymph nodes metastasis was higher than that in the group without lymph nodes metastasis. No significant relevance was found between the expression of OPN and other ultrasonographic features(include tumor size, margin and blood flow).
Conclusions
The expression levels of OPN in thyroid papillary carcinoma were higher than that in benign lesions and normal thyroid tissues. OPN may play an important role in the development of thyroid papillary carcinoma ; The expression levels of OPN mRNA was related with the presence of microcalcification and lymph nodes metastasis in ultrasonography. OPN may take part in the formation of the microcalcification, the ultrasonographic features can reflect the expression of OPN, so the biological behavior and prognosis of thyroid papillary carcinoma can be assessed by ultrasonographic features to some extent.
PART THREE Microvessel Density Determination in Thyroid Papillary Carcinoma and its Relationship with Ultrasonographic Features.
Background
Tumor angiogenesis plays an important role in its growth, invasion and metastasis, studying tumor angiogenesis in cancer research has been hot, measuring microvessel density (MVD) is now commonly used in evaluation of tumor angiogenesis, MVD can precisely reflect the angiogenesis in the tumor, has been regarded as an independent indicator for prediction of tumor prognosis. At present,in the majority of solid tumors , MVD was significantly increased and related to their invasiveness. CD34 is a new type of microvascular markers, which shows the vascular endothelial cells, the more sensitivity and specificity, ease of observation, with anti-CD34 antibody for microvessel staining can provide more useful and reliable information than the other markers.
At present, with the extensive use of ultrasonography ,color Doppler ultrasound has become one of the main inspection means for clinical diagnosis of thyroid disease, on the differential diagnosis of benign and malignant nodules has accumulated certain experience, but in some aspects of differential diagnosis of nodules is still controversial. In recent years , determination of MVD provides a new direction for the development of technology in thyroid nodular disease diagnosis, MVD accurately identifies tumor microvessel, and ultrasonic blood flow classification is the distribution of tumor blood vessels within the macro-test assessment, This study was to investigate the intrinsic link between the two ,and to provide more useful information for clinical diagnosis and assessment.
Objective
Through the observation of two-dimensional and color Doppler ultrasonography of 48 cases of papillary thyroid carcinoma and the control group, determination of MVD, compared with pathological results, evaluated color Doppler ultrasound and determination of MVD in the diagnosis of papillary thyroid carcinoma.
Methods
Color Doppler ultrasonic examination
Using ATL HDI-5000 and GE LOGIQ 9 color ultrasound diagnostic apparatus , observed and recorded the ultrasonography of 48 cases of papillary thyroid carcinoma. Two-dimensional ultrasonic observation of thyroid nodules included location, size, number, boundaries (fuzzy or clear), internal echo ,calcification (with particular attention to the existence of microcalcifications), neck lymph node swelling, and so on. Using color Doppler flow imaging (CDFI) and power Doppler imaging(PDI) to detect blood flow in each nodule, the nodule internal flow was divided into 4 levels(0-III) according to the Alder semi-quantitative methods.
Determination of MVD
With anti-CD34 monoclonal antibodies for immunohistochemical staining to detect the MVD in 48 cases of papillary thyroid carcinoma, 30 cases of benign thyroid lesions and 20 cases of normal thyroid tissue, made the capillaries counting in 200 time of fields (0.739mm~2) by two counters for each specimen for microvessel count using double-blind method, took the two's mean value for one specimen.
Results
Ultrasonic performance of Papillary thyroid carcinoma Papillary thyroid carcinoma in this group the most common sonographic performance showed irregular hypoechoic nodules, and nodules with fuzzy boundary , non-homogeneous and cluster "sand-like" strong echo, more than one strip flow points in the majority of nodules, often accompanied by lymph node metastasis. The flow in the nodules is divided into 4 levels according to the Alder semi-quantitative method, grade 0 9 cases , grade I 13 cases , grade II -III 26 cases.
MVD in benign and malignant thyroid nodules
MVD of papillary thyroid cancer tissue (126.8±42.1) is higher than that of benign thyroid lesions (95.2±38.5) and normal thyroid tissue (83.7±27.6)(p<0.05). The difference of MVD between benign thyroid lesions and normal thyroid tissue has no significances.
Papillary thyroid carcinoma power Doppler grading vs MVD
Mean MVD were: 97.3±35.4 (grade 0), 104.6±30.8 (grade I), 127.5±43.0 (grade II), 141.3±37.2 (grade III). By analysis of variance at all levels ,the numerical differences were significant (p<0.05),grade II was significantly higher than grade 0 and I, grade III were significantly higher than grade II, with the flow classification increased MVD was significantly higher.
Correlation between MVD and lymph node metastasis
MVD in lymph node metastasis positive group was 140.3±44.5, lymph node negative group was 116.0±36.7,by t-test, the difference between the two groups was statistically significant (p<0.05),showed that the MVD in papillary thyroid carcinoma lymph node metastasis positive group was higher than that of the negative group.
Correlation between papillary thyroid carcinoma sonographic features and MVD
MVD of 22 Larger nodules (≥2cm) was 139.4±37.8, 26 smaller nodules (<2cm) was 117.5±43.3, difference between the two groups was statistically significant (P<0.05), showed that larger nodules had higher MVD than smaller nodules. Nodular borders and gravel-like calcification were not significantly associated with MVD.
Conclusions
1. MVD of papillary thyroid carcinoma was higher than that of benign lesions and normal thyroid tissue.
2. Of ultrasonic features , the nodule size and lymph node metastasis were related to MVD significantly. The application of color Doppler Imaging accurately reflect the tumor microvessel situation.
3. Color Doppler ultrasound combined with the MVD determination will be able to more accurately reflect the tumor blood supply situation, and provide more information for clinical diagnosis and assessment.
引文
1.龚益,施秉银.甲状腺疾病的诊断治疗进展.国外医学内分泌分册,2001,21:174-176.
2.Franceschi S,Boyle P,Maissonneuve P.The epidemiology of thyroid carcinoma[J].Crit Rev Oncog,1993,4:25-52.
3.张武,梁建平.甲状腺疾病超声诊断进展[J].中华超声影像学杂志,1998,7(1):55-57.
4.施秉银.甲状腺结节和肿瘤的诊断、治疗与展望.中华内分泌代谢杂志,2003,19(2):83-85.
5.Shimamoto K,Endo T,Sakuma S,et al.Thyroid nodules:evaluation with color Doppler ultrasonography[J]J Ultrasound Med,1993,12(11):673-678.
6.Erik KA,Ellen M,Joseph O,et al.Thyroid nodule shape and prediction of malignancy[J].Thyroid,2004,14(11):953-958.
7.Hiroki S,Kazutaka H,Yoshimitsu H,et al.Distinct diagnostic criteria for ultrasonographic examination of papillary thyroid carconima:a multicenter study[J].Thyroid,2005,15(3):251-258.
8.Messina G,Viceconti N,Trinti B.Echotomographby and color Doppler in the diagnosis of thyroid carcinoma[J].Ann Ital Med Int.1996,11(4):263-267.
9.吴白云,郑宗英,邹利芝.甲状腺癌超声诊断及其误诊分析[J].中国超声医学杂志,1997,13(5):51-53.
10.侯锐,刘成国,王宝刚,等.甲状腺肿瘤超声图像特征与病理对照分析[J].中国超声医学杂志,1997,11(5):45-47.
11.Shodayu T,Haruki F,Naoko N,et al.Thyroid nodules:re-evaluation with ultrasound[J].J Clin Ultrasound,1995,23(2):179-184.
12.季正标,张晖,俞清.灰阶及彩色多普勒血流成像在甲状腺癌诊断中的应用[J],中国医学影像技术,2002,18(7):654-656.
13.刘洪枫,唐伟松,杨志英.甲状腺钙化性病灶与甲状腺癌.中国医学科学院学报,2003,25(5):626-629.
14.Khoo ML,Asa SL,Witterick IJ,et al.Thyroid calcification and its association with thyroid carcinoma.Head Neck,2002,24(7):651-655.
15.Kakkos SK,Scopa CD,Chalmoukis AK,et al.Relative risk of cancer in sonographically detected thyroid nodules with calcifications.J Clin Ultrasound,2000,28(7):347-352.
16.Hirota S,Ito A,Nagoshi J,et al.Expression of bone matrix protein messenger rribonucleic acids in human breast cancers.Possible involvement of osteopontin in development of calcifying foci.Lab Invest.1995,Jan;72(1):64-69.
17.Ghulam M Tunio,Seiichi Hirota,Shintaro Nomura,et al.Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer.Arch Pathol Lab Med,1998 Dec,122(12):1087-1090.
18.回允中,主译.阿克曼外科病理学(上卷).JUAN ROSAI.第1版.沈阳:辽宁教育出版社,1998.8.511-542.
19.Mary CF,Carol BB,Peter MD,et al.Can Color Doppler Sonography Aid in the Prediction of Malignancy of Thyroid Nodules[J]J Ult rasound Med,2003,22(2):127-131.
20.Gorges R,Eising A,Fotescu A,et al.Diagnostic Value of High-Resolution B-Mode and Power-Mode Sonography in the Follow-up of Thyroid Cancer[J].Euro J Ultrasound,2003,16(2):191-206.
21.Bryan KC,Terry SD,Ross McDougall,et al.Common and Uncommon Sonographic Features of Papillary Thyroid Carcinoma[J].J Ultrasound Med,2003,22(10):1083-1090.
22.陈文,张武,苗立英,等.甲状腺恶性肿瘤的二维及彩色多普勒超声征象及其临床意义[J].中国超声医学杂志,2000,16(7):495-497.
23.郭立英,徐文林,杨光,等.甲状腺恶性肿瘤的彩色多普勒及三维血流能量成像特征及其临床意义[J].中国超声医学杂志,2003,19(3):174-176.
24.Hussam M,Yousef B,Alzahrani AS,et al.Preoperative neck ultrasonographic mapping for persistent/recurrent papillary thyroid cancer.Word J Surg,2004,28(11):1110-1114.
25.Kessler A,Rappaport Y,Blank A,et al.Cystic appearance of cervical lymph nodes is characteristic of metastatic papillary thyroid carcinoma[J].J Clin Ultrasound.2003,31(1):21-25.
26.Sivanandan R,Soo KC.Pattern of cervical lymph node metastases from papillary carcinoma of the thyroid.Br J Surg,2001,88(9):1241-1244.
27.陈雨强.DNo期分化良好型甲状腺癌中淋巴结微转移灶的分布[J].国外医学:外科学分册,2002,29(5):302-303.
28.Noguchi M,Kumaki T,Taniya T,et al.Bilateral cervical lymph node metastases in well-differentiated thyroid cancer.Arch Surg,1990,125(6):804-806.
29.Kouvaraki MA,Shapiro SE,Fornage BD,et al.Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer.Surgery,2003,134(6):946-955.
1. Senger DR , Wirth DF , Hynes RO. Transformed mammalian cells secrete specific proteins and phosphoproteins[J] . Cell ,1979 ,16 (4) : 885-893.
2. Oldberg A , Franzen A , Heinegard D. Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci USA , 1986 , 83 :8819-8823.
3. Sharp JA, Sung V, Slavin J, et al. Tumor cells are the source of osteopontin and bone sialoprotein expressionin human breast cancer. Lab Invest, 1999, 79(7): 869-877.
4. Wang CS, Lin KH, Chen YF, et al. Overexpression of SPARC gene in human gastric carcinoma and clinic-pathologic significance. Br J Cancer, 2004,91(11): 1924-1930.
5. Shi juboN, Uede T, Kon S, et al. Vascular endothelial growth factors and osteopontin in tumor biology. Crit Rev Oncog, 2000, 11(2): 135-146.
6. Gilles C, Bassuk J. A., Pulyaeva H., et al. SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Res, 1998, 58(23): 5529-5536.
7. Akella Bellahene, Vincent Castronovo. Increased Expression of Osteonectin and Osteopontin, Two Bone Matrix Proteins, in Human Breast Cancer. American Journal of Pathology, 1995, 146(1):95-100.
8. Rudland PS, Platt-Higgins A, EI-Tanani M, et al. Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res. 2002, 15(1): 3417-3427.
9. Ariztia EV , Subbarao V , Solt DB , et al . Osteopontin contributes to heaptocyte growth factor-induced tumor growth and metastasis formation. Exp Cell Res , 2003 ,288 :257 - 267.
10.Ue T,Yolozaki H,Kitadai Y,et al.Co-expression of osteopontin and CD44v9 in gastric cancer.Int J Cancer,1998,79:127-132.
11.Coppola D,Szabo M,Boulware D,et al.Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies[J].Clin Cancer Res,2004,10:184-190.
12.Furger KA,Menon PK,Tuckl AB,et al.The functional and clinical roles of osteopontin in cancer and metastasis[J]Curr Mol Med,2001,1(5):621-632.
13.丁凌,郑树,曹江.大肠癌及其肝转移组织骨桥蛋白mRNA的表达.中华医学杂志,2000,82(14):970-973.
14.Schorge JO,Drake RD,Lee H,et al.Osteopontin as an adjunct to CA125 in detecting recurrent ovarian cancer.Clin Cancer Res,2004,10(10):3474-3478.
15.Wong TS,Kwong DL,Sham J,et al.Elevation of plasma osteopontin level in patients with undifferentiated nasopharyngeal carcinoma.Eur J Surg Oncol,2005,31(5):555-558.
16.Hu Z,Lin D,Yuan J,et al.Overexpression of osteopontin is associated with more aggressive phenotypes in human non-small cell lung cancer.Clin Cancer Res,2005,11(13):4646-4652.
17.Wai PY,Kuo PC.The role of osteopontin in tumor metastasis.J Surg Res,2004,121(2):228-241.
18.Guarino V,Faviana P,Salvatore G,et al.Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness.
19.Takano S,Tsuboi K,Tomono Y,et al.Tissue factor,osteopontin,alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression.Br J Cancer,2000,82(12):1967-1973.
20.Hirota S,Ito A,Nagoshi J,et al.Expression of bone matrix protein messenger ribonucleic acids in human breast cancers.Possible involvement of osteopontin in development of calcifying foci.Lab Invest.1995,72(1):64-69.
21.Bellahene A,Castronovo V,Expression of bone matrix protein in human breast cancer:potential roles in microcalcification formation and in the genesis of bone metastasis.Bull Cancer,199784(1):17-24.
22.Gillespie MT,Thomas RT,Pu ZY,et al.Calcitonin receptors,bone sialoprotein and osteopontin are expressed in primary breast cancers.Int J Cancer,1997,73(6):812-815.
23.李文生,宋志坚,赵淑民,等.骨桥蛋白和骨连接蛋白在冠状动脉粥样硬化斑块中的表达及与钙化的关系.解剖学杂志,2002,25(1):5-8.
24.Yamate T,Kohri K,Umekawa T,etal.Interaction between osteopontin on madin darby canine kidney cell membrance and calcium oxalate crystal.UrolInt,1999,62(2):81-86.
25.Tokes AM,Krausz J,Kulka J,et al,Role of osteopontin in the formation of microcalcifications in breast cancer.Orv Hetil,2002,143(31):1841-1846.
26.HirotaS,Ito A,Nagoshi J,et al.Expression of bone matrix protein messenger ribonucleic acids in human breast cancers.Possible involvement of osteopontin in development of calcifying foci.Lab Invest.1995,72(1):64-69.
27.杨光,张祥宏,张志刚,等.乳腺癌钼靶X线表现与癌组织骨桥蛋白、骨连接蛋白表达的相关性研究.临床放射学杂志,2006,25(2):134-137.
28.杨光,张祥宏,张静,等.乳腺癌组织中骨桥蛋白和骨连接蛋白的表达及其与微钙化形成的关系.中华放射学杂志,2006,40(9):953-956.
29.季正标,张晖,俞清,等.灰阶及彩色多普勒血流成像在甲状腺癌诊断中的应用.中国医学影像技术,2002,18(7):556-558.
30.刘洪枫,唐伟松,杨志英.甲状腺钙化性病灶与甲状腺癌.中国医学科学院 学报,2003, 25(5): 626-629.
31.Khoo ML, Asa SL, Witterick IJ, et al. Thyroid calcification and its association with thyroid carcinoma. Head Neck, 2002, 24(7): 651-655.
32. Kakkos SK, Scopa CD, Chalmoukis AK, et al. Relative risk of cancer in sonographically detected thyroid nodules with calcifications, J Clin Ultrasound, 2000, 28(7):347-352.
33. Fluge (?), Bruland O, Akslen LA, et al . Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer. Arch Pathol Lab Med. 1998 Dec;122(12):1087-90.
1.Weider N,Semple JP,Welch WR,et al.Tumour angiogenesis and metastasis correlation in invasive breast carcinoma.N Engl J Med,1991,324(1):1-8.
2.Horak ER,Leek R,Klenk N,et al.Angiogenesis,assessed by platelet/endothelial cell adhesion molecule antibodies,as indicator of node metastases and survival in breast cancer.Lancet,1992,340(8828):1120-1124.
3.Toi M,Kashitani J,Tominaga T.Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma.Int J Cancer,1993,55(3):371-374.
4.Tomisaki S,Ohno S,Ichiyoshi Y,et al.Microvessel quantification and its possible relation with liver metastasis in colorectal cancer.Cancer,1996,77(8):1722-1728.
5.Ichinoe M,Mikami T,Shiraishi H,et al.High microvascular density is correlated with high VEGF,NOS and COX-2 expression in penetrating growth-type early gastric carcinomas[J].Histopathology,2004;45(6):612 -618.
6.王瑛,王武.甲状腺囊性乳头状癌超声特征[J].中国超声医学杂志,1998,14(2):17-19.
7.Hatabu H,kassagi K,Yamamoto,et al.Cystic papillary carcinoma of the thyroidgland:Anewsonographicsign[J]Clinical Radiology,1991,43:121-123.
8.陈蒂荣,鲁树坤.甲状腺肿块的彩色多普勒血流频谱形态与病理对照研究[J].中国超声医学杂志,2004,20(4):257-259.
9.梁建平,张武.彩色多普勒超声对甲状腺结节性病变诊断价值评价[J].基础医学与临床,1998,18(4):38-39.
10.龚新环,金亚萍.甲状腺病变的超声诊断探讨[J].中国超声医学杂志,1996,12(1):451-453.
11.James C,Starks M,Macgi D,et al.The use of imaging studies in the diagnosis and management of thyroid cancer and hyperpaka thyroidism[J].Surg Oncel Clin N Am,1999,8(1):1451-1453.
12.胡小涛,胡淑芳.甲状腺肿块的超声诊断进展[J].医学综述,2002,8 (3):1681-1683.
13.高勇,王杰军.肿瘤血管生长和缺氧诱导因子.国外医学肿瘤分册,2001,28(1):46-48.
14.Folkman J,Shiraz Y.Angiogenesis.J Biol,1992,267:603-606.
15.史景泉,陈易生主编.现代外科病理学[M].北京:人民军医出版社,1998:759.
16.董郡主编.病理学[M].第2版.北京:人民卫生出版社,1996:763.
17.李春海,李克勤.肿瘤微血管生成的机制与肿瘤侵袭和转移.中华肿瘤杂志,2000,22:181-183.
18.Passe TJ,Bluemke DA,Siegelman SS.Tumor angiogenesis:tutorial on implications for imaging.Radiology,1997,203:593-600.
19.Connolly DT,Heuvelman DM,Nelson R,et alTumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.J Clin Invest,1989,84:1470-1478.
20.Srivastava A,Laidler P,Davies RP,etc.The prognostic significance of tumor vascularity in intermediate thickness(0.76-4.0mm thick) skin melanoma.Am J Pathol,1998,133(2):419-423.
21.Tanigawa N,Amaya H,Mastumura M,etc.Tumor angiogenesis and mode of metastasisinpatientswithcolorectalcancer.CancerRes,1997,57(6):1043-1046.
22.O'Reilly MS,Holmtren L,Shing Y,etc.Angiostatin:A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma.Cell,1994,79(2):315-328.
23.Weidner N.Intratumor microvessel density as a prognostic factor in cancer.Am J Pathol,1995,147:9-19.
24.Weidner N,Folkman J,Pozza F,et al.Tumor angiogenesis:a new significant and independent prognostic indicator in early-stage breast carcinoma.J Natl Cancer Inst,1992,84(24):1875-1887.
25.Raspollini MR,Amunni G,Villanucci A,et al.Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma[J].Int J Gynecol Cancer,2004;14(5): 815-823.
26.Kirmaz C,Ozbilgin K,Yuksel H,et al.Increased expression of angiogenic markers in patients with seasonal allergic rhinitis[J].Eur Cytokine Netw,2004;315(4):317-322.
27.Fina L,Molgaard H,Robertson D,etc.Expression of the CD_(34) gene in vascular endothelial cells.Blood,1990,75(12):2417-2426.
28.Becker D,Bair HJ,Becker W,et al.Thyroid autonomy with color coded image-directed Doppler sonography:internal hypervascularization for the recognition of autonomous adenomas.J Clin Ultrasound.1997;25:63-67.
29.Clark KJ,Cronan JJ,Scola FH.Color Doppler sonography autonomic and physiologic assessment of the thyroid.J Clin Ultrasound.1995;23:215-223.
30.韩增辉,王全华,钱蕴秋.能量多普勒血流显像鉴别乳腺肿块及其临床应用价值.中国超声医学杂志,1997,13(1):34-36.
31.Todd D,Brian J,David A,et al.Evaluation of palpable breast masses with color Doppler sonography and gray scale imaging.J Ultrasound Med,1998,17:110-111.
32.荣雪余,孙强,姜玉新.能量多普勒超声造影在乳腺肿瘤诊断中的应用研究.中华超声影像学杂志,2002,11:669-672.
33.Yang QF,Barbareschi M,Moil I,et al.Prognostic value of thymidine phosphorylase expression in breast carcinoma.International Journal of Cancer,2002,97(4):512-517.
34.Vakkala M,Kahlos K,Lakari E,et al.Inducible nitric oxide synthase expression,apoptosis,and angiogenesis in situ and invasive breast carcinomas.Clinical Cancer Research,2000,6(6):2408-2416.
35.Takahashi Y,Kitadai Y,Bucana CD,etc.Expression of vascular endothelial growth factor and its receptor,KDR,correlates with vascularity,metastasis and proliferation of human colon cancer.Cancer Res,1995,55(18):3964-3968.
36.TakahashiY,Bucana CD,Cleary K,etc.p53,vessel count,and vascular endothelial growth factor expression in human colon cancer.Int J Cancer,1998,79(1):34-38.
37.Meada K,Chung YS,OgawaY,etc.Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer, 1996,77(5):858-863.
38. O'Brien T, Cranston D, Fuggle S, etc. Different angiogenic pathways characterize superficial and invasive bladder cancer. Cancer Res, 1995, 55(3):510-513.
39. Claffey KP, Brown IF, Aguila IF, etc. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res, 1996, 56(1):172-181.
40.Stabenow E, Tavares MR, Ab'Saber AM,et al. Angiogenesis as an indicator of metastatic potential in papillary thyroid carcinoma. Clinics. 2005 Jun;60 (3):233-240.
41.Akslen LA, Livolsi VA.Increased angiogenesis in papillary thyroid carcinoma but lack of prognostic importance.Hum Pathol. 2000 Apr;31(4):439-442.
42. Jebreel A, England J, Bedford K,et al. Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseases. Int J Exp Pathol. 2007 Aug;88(4):271-277.
1. Lin YH , Yang-Yen HF. The osteopontin -CD44 survival signal involves activation of the phosphatidy linositol 3-kinase/Akt signaling pathway. J Biol Chem, 2001,276 :46024 - 46030.
2. Wai PY, Kuo PC. The role of osteopontin in tumor metastasis. J Surg Res, 2004,121 :228-241.
3. Senger DR ,Wirth DF ,Hynes RO. Transformed mammalian cells secrete specific proteins and phosphoproteins[J] Cell, 1979,16 (4):885-893.
4. Zhang J , Talahashi K, Takahashi F , et al. Differential osteopontin expression in lung cancer. Cancer Lett, 2001 ,171 :215 - 222.
5. Weber GF. The metastasis gene osteopontin : a candidate target for cancer therapy. Biochimica te Biophysica Acta, 2001,1552 :61 - 85.
6. Hirama M, Takahashi F , Takahashi K, et al . Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth. Cancer Lett, 2003 ,198 :107 -117.
7. Gotoh M, Sakamoto M, Kanetaka K, et al . Overexpression of osteopontin in hepatocellular carcinoma. Pathol Int, 2002 ,52 :19 - 24.
8. Pan HW, Ou YH , Peng SY, et al. Overexpression of osteopontin is associated with intrahepatic metastasis , early recurrence ,and poorer prognosis of surgically resected hepatocellular carcinoma. Cancer, 2003 ,98 :119-127.
9. Chang PL , Cao M, Hicks P. Osteopontin induction is required for tumor promoter-induced transformation of preneoplastic mouse cells. Carcino genesis , 2003,24:1749-1758.
10. Coppola D , Szabo M, Boulware D , et al. Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res, 2004,10 :184 -190.
11. Terashi T, Aishima S , Taguchi K, et al. Decreased expression of osteopontin is related to tumor aggressiveness and clinical outcome of intrahepatic cholangiocarcinoma. Liver Int, 2004 ,24 :38 - 45.
12. Tahara E. Molecular aspects of invasion and metastasis of stomach cancer. Verh Dtsch Ges Pathol, 2000,84 :43 - 49.
13. Ue T , Yolozaki H , Kitadai Y, et al . Co-expression of osteopontin and CD44v9 in gastric cancer. Int J Cancer, 1998 ,79 :127 -132.
14. Maeng HY, Choi DK, Takeuchi M, et al . Appearance of osteopontin -expressing fibroblastic cells in early rat stomach carcinogenesis and stomach tumors induced with N-methyl-N'-nitro-N- nitro- soguanidine. Jpn J Cancer Res, 2002 ,93 :960 - 967.
15. Weber GF , Zawaideh S , Hikita S , et al . Phosphorylation macrophage migration and activation [J]. J Leukoc Biol ,2002 ,72(4) :752-761.
16. Rosen DG, Wang L, Atkinson YN, et al. Potential makers that complement expression of CA125 in epithelial ovarian cancer . Gynecol Oncol, 2005. 99: 267-277.
17. Maki M ,Hirota S,Kaneko Y, et al. Expression of osteopontin messenger RNA by macrophages in ovarian serous papillary cyst adenocarcinoma: a possible association with calcification of psammoma bodies . Pathol Int. 2000. 50: 531-535.
18. Fisher LW , Jain A, Taybeck M, et al. Small integrin binding ligand N-linked glycoprotein gene family expression in different cancers. Clin Cancer Res. 2004. 10: 8501-8511.
19. O'NeiU CJ. Deavers MT,Malpica A, et al. An immuno—histochemical comparison between low-grade and high-grade ovarian serous carcinomas : significantly higher expression of p53, MIB1, BCI2, HER-2/neu, and C—KIT in hjgh—grade neoplasms. Am J Surg Pathol, 2005, 29: 1034-1041.
20. Bellahene A , Cast ronovo C. Increased expression of osteonectin and osteopontin , two bone matrix proteins in human breast cancer [J] . Am J Pat hol ,1995 ,146 (1):95-100.
21. Hirota S , Ito A , Nagoshi J , et al . Expression of bone matrix protein messenger ribonucleic acids in human breast cancers. Possible involvement of osteopontin in development of calcifying foci [J] . Lab Invest ,1995 ,72 (1):64-69.
22. Tokes AM , Krausz J , Kulka J , et al. Role of osteopontin in the formation of microcalcifications in breast cancer [J]. Orv Hetil, 2002,143 (31) :1841-1846.
23.Yang G, Zhang XH , Zhang ZG, et al . Correlation of X-ray features in mammography and expression of OPN and ON of breast carcinoma[J] . J Clin Radiol,2006,25(2):134-137.
24.Rudland PS,Platt Higgins A,E1 Tanani M . et al. Prognostic significance of the metastasis associated protein osteopontin in human breast cancer[J]. Cancer Res, 2002. 1 5(1): 3417-3427.
25. Kim YW, Park YK, Lee J , et al. Expression of osteopontin and osteonectin in breast cancer [J]. J Korean Med ,1998 ,13 (6) :652-657.
26. Tuck AB , Chambers AF. The role of osteopontin in breast cancer : clinical and experimental studies. Mammary Gland Biol Neoplasia , 2001 ,6 : 419 - 429.
27. Le QT ,Sutphin PD ,Taychaudhuri S , et al. Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas[J]. Clin Cancer Res ,2003 ,9 (1) :59-67.
28. Petrik D ,Cao H ,Zhu Y, et al. An expanded study of the relationship between osteopontin ,tumor PO2 and prognosis in head and neck squamous cell carcinomas[J]. J Clin Oncol ,2005 ,23(16s) :5521.
29. Celetti A ,Testa D ,Staibano S , et al . Overexpression of the cytokine osteopontin identifies aggressive latyngesl squamous cell carcinomas and enhances carcinoma cell proliferation and invasiveness[J ] . Clin Cancer Res ,2005 ,11(22) :8019-8027.
30. Takano T ,Haseqawa Y,Matsuzuka F , et al . Gene expression profiles in thyroid carcinomas[J] .Br J Cancer ,2000,83(11) :1495-1502.
31. Guarino V ,Faviana P ,Salvatore G, et al . Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness [J]. J Clin Endocrinol Metab , 2005 , 90 (9): 5270-5278.
32. Ghulam M Tunio, Seiichi Hirota, Shintaro Nomura, et al .Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer. Arch Pathol Lab Med, 1998 Dec, 122 (12) :1087-1090.
33. Yeatman TJ ,Chambers AF. Osteopontin and colon cancer progression [J] . Clin Exp Metastasis ,2003 ,20(1) :85-90.
34. Guo H , Cai CO , Schroeder RA , et al. Osteopontin is a negative feed back regulator of nitric oxide synthesis in murine macrophages. J Immunol , 2001,166:1079-1086.
35. Bautista DS , Xuan JW, Hota C , et al . Inhibition of Arg-Gly-Asp (RGD)-mediated cell adhesion to osteopontin by a monoclonal antibody against osteopontin. Biol Chem, 1994 ,269 .23280 - 23285.
36. Hirama M, Takahashi F , Takahashi K, et al . Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth. Cancer Lett, 2003 ,198 :107 -117.
37. Overgaard J ,Eriksen JG,Nordsmark M, et al. Plasma osteopontin , hypoxia , and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer : results from the DAHANCA 5 randomised double-bind placcbo-controlled trial [J ]. Lancet Oncol ,2005 ,6 (10): 757-764.
38. Rudland PS , Platt-Higgins A , EI-Tanani M , et al. Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer [J ] . Cancer Res ,2002 ,15(1) :3417-3427.
39. Donati V , Boldrini L , Dell'Omodarme M, et al. Osteopontin expression and prognostic significance in non-small cell lung cancer. Clin Cancer Res , 2005,11 :6459-6465.
[1]Oldberg A,Franzen A,Heinegard D.Cloning and sequence analysis ofrat bone sialoprotein(osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence.Proc Natl Acad Sci USA,1986,83:8819-8823.
[2]Wai PY,Kuo PC.The role of osteopontin in tumor metastasis.J Surg Res,2004,121:228-241.
[3]贺斌,刘银坤,汤钊猷,等.肝癌中骨桥蛋白表达的临床意义.中华肝脏病杂志,1998,4:208-210.
[4]Rudland PS,Higgins AP,Tanani ME,et al.Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer.Cancer Res,2002,62:3417-3427.
[5]Ariztia EV,Subbarao V,Solt DB,et al.Osteopontin contributes to heaptocyte growth factor-induced tumor growth and metastasis formation.Exp Cell Res,2003,288:257-267.
[6]Ue T,Yolozaki H,Kitadai Y,et al.Co-expression of osteopontin and CD44v9 in gastric cancer.Int J Cancer,1998,79:127-132.
[7]Guarino V,Faviana P,Salvatore G,et al.Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness.J Clin Endocrinol Metab.2005 Sep;90(9):5270-5278.
[8]季正标,张晖,俞清,等.灰阶及彩色多普勒血流成像在甲状腺癌诊断中的应用.中国医学影像技术,2002,18(7):556-558.
[9]刘洪枫,唐伟松,杨志英.甲状腺钙化性病灶与甲状腺癌.中国医学科学院学报,2003,25(5):626-629.
[10]Khoo ML,Asa SL,Witterick IJ,et al.T hyroid calcification and its association with thyroid carcinoma.HeM Neck,2002,24(7):651-655.
[11]Kakkos SK,Scopa CD,Chalmoukis AK,et al.Relative risk of cancer in sonographically detected thyroid nodules with calcifications,J Clin Ultrasound,2000,28(7):347-352.
[12]Hirota S,Ito A,Nagoshi J,et al.Expression of bone matrix protein messenger rribonucleic acids in human breast cancers.Possible involvement of osteopontin in development of calcifying foci.Lab Invest.1995,Jan;72(1):64-69.
[13]Fluge φ,Bruland O,Akslen LA,et al.Possible re lation of osteopontin to development of psammoma bodies in human papillary thyroid cancer.Arch Pathol Lab Med.1998 Dec;122(12):1087-90.
1.Horak ER,Leek R, Klenk N , et al. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet, 1992, 340 (8828) : 1120-1124.
2.ToiM , Kashitani J , Tominaga T.Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma.Int J Cancer, 1993,55(3) :371-374.
3.Tomisaki S, Ohno S, Ichiyoshi Y, et al. Microvessel quantification and its possible relation with liver metastasis in colorectal cancer.Cancer, 1996, 77 (8): 1722-1728.
4.Ichinoe M, Mikami T, Shiraishi H, et al. High microvascular density is correlated with high VEGF, NOS and COX-2 expression in penetrating growth-type early gastric carcinomas [J]. Histopathology, 2004; 45 (6) : 612 - 618.
5.Weidner N. Intratumor microvessel density as a prognostic factor in cancer . Am J Pathol, 1995 ,147:9-19.
6.Weidner N , Folkman J , Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst, 1992, 84 (24): 1875-1887.
7.Raspollini MR, Amunni G, Villanucci A, et al. Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma [J]. Int J Gynecol Cancer, 2004; 14 (5) : 815-823.
8.Passe TJ ,Bluemke DA , Siegelman SS. Tumor angiogenesis : tutorial on implications for imaging. Radiology ,1997 ,203 .593-600.
9.Connolly DT , Heuvelman DM , Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest ,1989,84 :1470-1478.
10.Kirmaz C, Ozbilgin K, Yuksel H, et al. Increased expression of angiogenic markers in patients with seasonal allergic rhinitis [ J ]. Eur Cytokine Netw, 2004; 315 (4): 317-322.
11. Fina L, Molgaard H,Robertson D, etc. Expression of the CD_(34) gene in vascular endothelial cells. Blood, 1990,75(12):2417-2426.
12.Stabenow E, Tavares MR, Ab'Saber AM,et al. Angiogenesis as an indicator of metastatic potential in papillary thyroid carcinoma. Clinics. 2005 Jun;60(3):233-40.
13.Akslen LA, Livolsi VA.Increased angiogenesis in papillary thyroid carcinoma but lack of prognostic importance.Hum Pathol. 2000 Apr;31(4):439-442.
14.Todd D ,Brian J ,David A ,et al . Evaluation of palpable breast masses with color Doppler sonography and gray scale imaging. J Ultrasound Med , 1998,17:110-111.
15.Clark KJ,Cronan JJ,Scola FH.Color Doppler sonography autonomic and physiologic assessment of the thyroid.J Clin Ultrasound. 1995;23:215-223.
16.Folkman J , Shing Y.Angiogenesis.J Biol, 1992, 267: 603-606.
17.Jebreel A, England J, Bedford K,et al. Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseases.Int J Exp Pathol. 2007 Aug;88(4):271-277.
2.Franceschi S,Boyle P,Maissonneuve P.The epidemiology of thyroid carcinoma[J].Crit Rev Oncog,1993,4:25-52.
3.张武,梁建平.甲状腺疾病超声诊断进展[J].中华超声影像学杂志,1998,7(1):55-57.
4.施秉银.甲状腺结节和肿瘤的诊断、治疗与展望.中华内分泌代谢杂志,2003,19(2):83-85.
5.Shimamoto K,Endo T,Sakuma S,et al.Thyroid nodules:evaluation with color Doppler ultrasonography[J]J Ultrasound Med,1993,12(11):673-678.
6.Erik KA,Ellen M,Joseph O,et al.Thyroid nodule shape and prediction of malignancy[J].Thyroid,2004,14(11):953-958.
7.Hiroki S,Kazutaka H,Yoshimitsu H,et al.Distinct diagnostic criteria for ultrasonographic examination of papillary thyroid carconima:a multicenter study[J].Thyroid,2005,15(3):251-258.
8.Messina G,Viceconti N,Trinti B.Echotomographby and color Doppler in the diagnosis of thyroid carcinoma[J].Ann Ital Med Int.1996,11(4):263-267.
9.吴白云,郑宗英,邹利芝.甲状腺癌超声诊断及其误诊分析[J].中国超声医学杂志,1997,13(5):51-53.
10.侯锐,刘成国,王宝刚,等.甲状腺肿瘤超声图像特征与病理对照分析[J].中国超声医学杂志,1997,11(5):45-47.
11.Shodayu T,Haruki F,Naoko N,et al.Thyroid nodules:re-evaluation with ultrasound[J].J Clin Ultrasound,1995,23(2):179-184.
12.季正标,张晖,俞清.灰阶及彩色多普勒血流成像在甲状腺癌诊断中的应用[J],中国医学影像技术,2002,18(7):654-656.
13.刘洪枫,唐伟松,杨志英.甲状腺钙化性病灶与甲状腺癌.中国医学科学院学报,2003,25(5):626-629.
14.Khoo ML,Asa SL,Witterick IJ,et al.Thyroid calcification and its association with thyroid carcinoma.Head Neck,2002,24(7):651-655.
15.Kakkos SK,Scopa CD,Chalmoukis AK,et al.Relative risk of cancer in sonographically detected thyroid nodules with calcifications.J Clin Ultrasound,2000,28(7):347-352.
16.Hirota S,Ito A,Nagoshi J,et al.Expression of bone matrix protein messenger rribonucleic acids in human breast cancers.Possible involvement of osteopontin in development of calcifying foci.Lab Invest.1995,Jan;72(1):64-69.
17.Ghulam M Tunio,Seiichi Hirota,Shintaro Nomura,et al.Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer.Arch Pathol Lab Med,1998 Dec,122(12):1087-1090.
18.回允中,主译.阿克曼外科病理学(上卷).JUAN ROSAI.第1版.沈阳:辽宁教育出版社,1998.8.511-542.
19.Mary CF,Carol BB,Peter MD,et al.Can Color Doppler Sonography Aid in the Prediction of Malignancy of Thyroid Nodules[J]J Ult rasound Med,2003,22(2):127-131.
20.Gorges R,Eising A,Fotescu A,et al.Diagnostic Value of High-Resolution B-Mode and Power-Mode Sonography in the Follow-up of Thyroid Cancer[J].Euro J Ultrasound,2003,16(2):191-206.
21.Bryan KC,Terry SD,Ross McDougall,et al.Common and Uncommon Sonographic Features of Papillary Thyroid Carcinoma[J].J Ultrasound Med,2003,22(10):1083-1090.
22.陈文,张武,苗立英,等.甲状腺恶性肿瘤的二维及彩色多普勒超声征象及其临床意义[J].中国超声医学杂志,2000,16(7):495-497.
23.郭立英,徐文林,杨光,等.甲状腺恶性肿瘤的彩色多普勒及三维血流能量成像特征及其临床意义[J].中国超声医学杂志,2003,19(3):174-176.
24.Hussam M,Yousef B,Alzahrani AS,et al.Preoperative neck ultrasonographic mapping for persistent/recurrent papillary thyroid cancer.Word J Surg,2004,28(11):1110-1114.
25.Kessler A,Rappaport Y,Blank A,et al.Cystic appearance of cervical lymph nodes is characteristic of metastatic papillary thyroid carcinoma[J].J Clin Ultrasound.2003,31(1):21-25.
26.Sivanandan R,Soo KC.Pattern of cervical lymph node metastases from papillary carcinoma of the thyroid.Br J Surg,2001,88(9):1241-1244.
27.陈雨强.DNo期分化良好型甲状腺癌中淋巴结微转移灶的分布[J].国外医学:外科学分册,2002,29(5):302-303.
28.Noguchi M,Kumaki T,Taniya T,et al.Bilateral cervical lymph node metastases in well-differentiated thyroid cancer.Arch Surg,1990,125(6):804-806.
29.Kouvaraki MA,Shapiro SE,Fornage BD,et al.Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer.Surgery,2003,134(6):946-955.
1. Senger DR , Wirth DF , Hynes RO. Transformed mammalian cells secrete specific proteins and phosphoproteins[J] . Cell ,1979 ,16 (4) : 885-893.
2. Oldberg A , Franzen A , Heinegard D. Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci USA , 1986 , 83 :8819-8823.
3. Sharp JA, Sung V, Slavin J, et al. Tumor cells are the source of osteopontin and bone sialoprotein expressionin human breast cancer. Lab Invest, 1999, 79(7): 869-877.
4. Wang CS, Lin KH, Chen YF, et al. Overexpression of SPARC gene in human gastric carcinoma and clinic-pathologic significance. Br J Cancer, 2004,91(11): 1924-1930.
5. Shi juboN, Uede T, Kon S, et al. Vascular endothelial growth factors and osteopontin in tumor biology. Crit Rev Oncog, 2000, 11(2): 135-146.
6. Gilles C, Bassuk J. A., Pulyaeva H., et al. SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Res, 1998, 58(23): 5529-5536.
7. Akella Bellahene, Vincent Castronovo. Increased Expression of Osteonectin and Osteopontin, Two Bone Matrix Proteins, in Human Breast Cancer. American Journal of Pathology, 1995, 146(1):95-100.
8. Rudland PS, Platt-Higgins A, EI-Tanani M, et al. Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res. 2002, 15(1): 3417-3427.
9. Ariztia EV , Subbarao V , Solt DB , et al . Osteopontin contributes to heaptocyte growth factor-induced tumor growth and metastasis formation. Exp Cell Res , 2003 ,288 :257 - 267.
10.Ue T,Yolozaki H,Kitadai Y,et al.Co-expression of osteopontin and CD44v9 in gastric cancer.Int J Cancer,1998,79:127-132.
11.Coppola D,Szabo M,Boulware D,et al.Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies[J].Clin Cancer Res,2004,10:184-190.
12.Furger KA,Menon PK,Tuckl AB,et al.The functional and clinical roles of osteopontin in cancer and metastasis[J]Curr Mol Med,2001,1(5):621-632.
13.丁凌,郑树,曹江.大肠癌及其肝转移组织骨桥蛋白mRNA的表达.中华医学杂志,2000,82(14):970-973.
14.Schorge JO,Drake RD,Lee H,et al.Osteopontin as an adjunct to CA125 in detecting recurrent ovarian cancer.Clin Cancer Res,2004,10(10):3474-3478.
15.Wong TS,Kwong DL,Sham J,et al.Elevation of plasma osteopontin level in patients with undifferentiated nasopharyngeal carcinoma.Eur J Surg Oncol,2005,31(5):555-558.
16.Hu Z,Lin D,Yuan J,et al.Overexpression of osteopontin is associated with more aggressive phenotypes in human non-small cell lung cancer.Clin Cancer Res,2005,11(13):4646-4652.
17.Wai PY,Kuo PC.The role of osteopontin in tumor metastasis.J Surg Res,2004,121(2):228-241.
18.Guarino V,Faviana P,Salvatore G,et al.Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness.
19.Takano S,Tsuboi K,Tomono Y,et al.Tissue factor,osteopontin,alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression.Br J Cancer,2000,82(12):1967-1973.
20.Hirota S,Ito A,Nagoshi J,et al.Expression of bone matrix protein messenger ribonucleic acids in human breast cancers.Possible involvement of osteopontin in development of calcifying foci.Lab Invest.1995,72(1):64-69.
21.Bellahene A,Castronovo V,Expression of bone matrix protein in human breast cancer:potential roles in microcalcification formation and in the genesis of bone metastasis.Bull Cancer,199784(1):17-24.
22.Gillespie MT,Thomas RT,Pu ZY,et al.Calcitonin receptors,bone sialoprotein and osteopontin are expressed in primary breast cancers.Int J Cancer,1997,73(6):812-815.
23.李文生,宋志坚,赵淑民,等.骨桥蛋白和骨连接蛋白在冠状动脉粥样硬化斑块中的表达及与钙化的关系.解剖学杂志,2002,25(1):5-8.
24.Yamate T,Kohri K,Umekawa T,etal.Interaction between osteopontin on madin darby canine kidney cell membrance and calcium oxalate crystal.UrolInt,1999,62(2):81-86.
25.Tokes AM,Krausz J,Kulka J,et al,Role of osteopontin in the formation of microcalcifications in breast cancer.Orv Hetil,2002,143(31):1841-1846.
26.HirotaS,Ito A,Nagoshi J,et al.Expression of bone matrix protein messenger ribonucleic acids in human breast cancers.Possible involvement of osteopontin in development of calcifying foci.Lab Invest.1995,72(1):64-69.
27.杨光,张祥宏,张志刚,等.乳腺癌钼靶X线表现与癌组织骨桥蛋白、骨连接蛋白表达的相关性研究.临床放射学杂志,2006,25(2):134-137.
28.杨光,张祥宏,张静,等.乳腺癌组织中骨桥蛋白和骨连接蛋白的表达及其与微钙化形成的关系.中华放射学杂志,2006,40(9):953-956.
29.季正标,张晖,俞清,等.灰阶及彩色多普勒血流成像在甲状腺癌诊断中的应用.中国医学影像技术,2002,18(7):556-558.
30.刘洪枫,唐伟松,杨志英.甲状腺钙化性病灶与甲状腺癌.中国医学科学院 学报,2003, 25(5): 626-629.
31.Khoo ML, Asa SL, Witterick IJ, et al. Thyroid calcification and its association with thyroid carcinoma. Head Neck, 2002, 24(7): 651-655.
32. Kakkos SK, Scopa CD, Chalmoukis AK, et al. Relative risk of cancer in sonographically detected thyroid nodules with calcifications, J Clin Ultrasound, 2000, 28(7):347-352.
33. Fluge (?), Bruland O, Akslen LA, et al . Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer. Arch Pathol Lab Med. 1998 Dec;122(12):1087-90.
1.Weider N,Semple JP,Welch WR,et al.Tumour angiogenesis and metastasis correlation in invasive breast carcinoma.N Engl J Med,1991,324(1):1-8.
2.Horak ER,Leek R,Klenk N,et al.Angiogenesis,assessed by platelet/endothelial cell adhesion molecule antibodies,as indicator of node metastases and survival in breast cancer.Lancet,1992,340(8828):1120-1124.
3.Toi M,Kashitani J,Tominaga T.Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma.Int J Cancer,1993,55(3):371-374.
4.Tomisaki S,Ohno S,Ichiyoshi Y,et al.Microvessel quantification and its possible relation with liver metastasis in colorectal cancer.Cancer,1996,77(8):1722-1728.
5.Ichinoe M,Mikami T,Shiraishi H,et al.High microvascular density is correlated with high VEGF,NOS and COX-2 expression in penetrating growth-type early gastric carcinomas[J].Histopathology,2004;45(6):612 -618.
6.王瑛,王武.甲状腺囊性乳头状癌超声特征[J].中国超声医学杂志,1998,14(2):17-19.
7.Hatabu H,kassagi K,Yamamoto,et al.Cystic papillary carcinoma of the thyroidgland:Anewsonographicsign[J]Clinical Radiology,1991,43:121-123.
8.陈蒂荣,鲁树坤.甲状腺肿块的彩色多普勒血流频谱形态与病理对照研究[J].中国超声医学杂志,2004,20(4):257-259.
9.梁建平,张武.彩色多普勒超声对甲状腺结节性病变诊断价值评价[J].基础医学与临床,1998,18(4):38-39.
10.龚新环,金亚萍.甲状腺病变的超声诊断探讨[J].中国超声医学杂志,1996,12(1):451-453.
11.James C,Starks M,Macgi D,et al.The use of imaging studies in the diagnosis and management of thyroid cancer and hyperpaka thyroidism[J].Surg Oncel Clin N Am,1999,8(1):1451-1453.
12.胡小涛,胡淑芳.甲状腺肿块的超声诊断进展[J].医学综述,2002,8 (3):1681-1683.
13.高勇,王杰军.肿瘤血管生长和缺氧诱导因子.国外医学肿瘤分册,2001,28(1):46-48.
14.Folkman J,Shiraz Y.Angiogenesis.J Biol,1992,267:603-606.
15.史景泉,陈易生主编.现代外科病理学[M].北京:人民军医出版社,1998:759.
16.董郡主编.病理学[M].第2版.北京:人民卫生出版社,1996:763.
17.李春海,李克勤.肿瘤微血管生成的机制与肿瘤侵袭和转移.中华肿瘤杂志,2000,22:181-183.
18.Passe TJ,Bluemke DA,Siegelman SS.Tumor angiogenesis:tutorial on implications for imaging.Radiology,1997,203:593-600.
19.Connolly DT,Heuvelman DM,Nelson R,et alTumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.J Clin Invest,1989,84:1470-1478.
20.Srivastava A,Laidler P,Davies RP,etc.The prognostic significance of tumor vascularity in intermediate thickness(0.76-4.0mm thick) skin melanoma.Am J Pathol,1998,133(2):419-423.
21.Tanigawa N,Amaya H,Mastumura M,etc.Tumor angiogenesis and mode of metastasisinpatientswithcolorectalcancer.CancerRes,1997,57(6):1043-1046.
22.O'Reilly MS,Holmtren L,Shing Y,etc.Angiostatin:A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma.Cell,1994,79(2):315-328.
23.Weidner N.Intratumor microvessel density as a prognostic factor in cancer.Am J Pathol,1995,147:9-19.
24.Weidner N,Folkman J,Pozza F,et al.Tumor angiogenesis:a new significant and independent prognostic indicator in early-stage breast carcinoma.J Natl Cancer Inst,1992,84(24):1875-1887.
25.Raspollini MR,Amunni G,Villanucci A,et al.Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma[J].Int J Gynecol Cancer,2004;14(5): 815-823.
26.Kirmaz C,Ozbilgin K,Yuksel H,et al.Increased expression of angiogenic markers in patients with seasonal allergic rhinitis[J].Eur Cytokine Netw,2004;315(4):317-322.
27.Fina L,Molgaard H,Robertson D,etc.Expression of the CD_(34) gene in vascular endothelial cells.Blood,1990,75(12):2417-2426.
28.Becker D,Bair HJ,Becker W,et al.Thyroid autonomy with color coded image-directed Doppler sonography:internal hypervascularization for the recognition of autonomous adenomas.J Clin Ultrasound.1997;25:63-67.
29.Clark KJ,Cronan JJ,Scola FH.Color Doppler sonography autonomic and physiologic assessment of the thyroid.J Clin Ultrasound.1995;23:215-223.
30.韩增辉,王全华,钱蕴秋.能量多普勒血流显像鉴别乳腺肿块及其临床应用价值.中国超声医学杂志,1997,13(1):34-36.
31.Todd D,Brian J,David A,et al.Evaluation of palpable breast masses with color Doppler sonography and gray scale imaging.J Ultrasound Med,1998,17:110-111.
32.荣雪余,孙强,姜玉新.能量多普勒超声造影在乳腺肿瘤诊断中的应用研究.中华超声影像学杂志,2002,11:669-672.
33.Yang QF,Barbareschi M,Moil I,et al.Prognostic value of thymidine phosphorylase expression in breast carcinoma.International Journal of Cancer,2002,97(4):512-517.
34.Vakkala M,Kahlos K,Lakari E,et al.Inducible nitric oxide synthase expression,apoptosis,and angiogenesis in situ and invasive breast carcinomas.Clinical Cancer Research,2000,6(6):2408-2416.
35.Takahashi Y,Kitadai Y,Bucana CD,etc.Expression of vascular endothelial growth factor and its receptor,KDR,correlates with vascularity,metastasis and proliferation of human colon cancer.Cancer Res,1995,55(18):3964-3968.
36.TakahashiY,Bucana CD,Cleary K,etc.p53,vessel count,and vascular endothelial growth factor expression in human colon cancer.Int J Cancer,1998,79(1):34-38.
37.Meada K,Chung YS,OgawaY,etc.Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer, 1996,77(5):858-863.
38. O'Brien T, Cranston D, Fuggle S, etc. Different angiogenic pathways characterize superficial and invasive bladder cancer. Cancer Res, 1995, 55(3):510-513.
39. Claffey KP, Brown IF, Aguila IF, etc. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res, 1996, 56(1):172-181.
40.Stabenow E, Tavares MR, Ab'Saber AM,et al. Angiogenesis as an indicator of metastatic potential in papillary thyroid carcinoma. Clinics. 2005 Jun;60 (3):233-240.
41.Akslen LA, Livolsi VA.Increased angiogenesis in papillary thyroid carcinoma but lack of prognostic importance.Hum Pathol. 2000 Apr;31(4):439-442.
42. Jebreel A, England J, Bedford K,et al. Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseases. Int J Exp Pathol. 2007 Aug;88(4):271-277.
1. Lin YH , Yang-Yen HF. The osteopontin -CD44 survival signal involves activation of the phosphatidy linositol 3-kinase/Akt signaling pathway. J Biol Chem, 2001,276 :46024 - 46030.
2. Wai PY, Kuo PC. The role of osteopontin in tumor metastasis. J Surg Res, 2004,121 :228-241.
3. Senger DR ,Wirth DF ,Hynes RO. Transformed mammalian cells secrete specific proteins and phosphoproteins[J] Cell, 1979,16 (4):885-893.
4. Zhang J , Talahashi K, Takahashi F , et al. Differential osteopontin expression in lung cancer. Cancer Lett, 2001 ,171 :215 - 222.
5. Weber GF. The metastasis gene osteopontin : a candidate target for cancer therapy. Biochimica te Biophysica Acta, 2001,1552 :61 - 85.
6. Hirama M, Takahashi F , Takahashi K, et al . Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth. Cancer Lett, 2003 ,198 :107 -117.
7. Gotoh M, Sakamoto M, Kanetaka K, et al . Overexpression of osteopontin in hepatocellular carcinoma. Pathol Int, 2002 ,52 :19 - 24.
8. Pan HW, Ou YH , Peng SY, et al. Overexpression of osteopontin is associated with intrahepatic metastasis , early recurrence ,and poorer prognosis of surgically resected hepatocellular carcinoma. Cancer, 2003 ,98 :119-127.
9. Chang PL , Cao M, Hicks P. Osteopontin induction is required for tumor promoter-induced transformation of preneoplastic mouse cells. Carcino genesis , 2003,24:1749-1758.
10. Coppola D , Szabo M, Boulware D , et al. Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res, 2004,10 :184 -190.
11. Terashi T, Aishima S , Taguchi K, et al. Decreased expression of osteopontin is related to tumor aggressiveness and clinical outcome of intrahepatic cholangiocarcinoma. Liver Int, 2004 ,24 :38 - 45.
12. Tahara E. Molecular aspects of invasion and metastasis of stomach cancer. Verh Dtsch Ges Pathol, 2000,84 :43 - 49.
13. Ue T , Yolozaki H , Kitadai Y, et al . Co-expression of osteopontin and CD44v9 in gastric cancer. Int J Cancer, 1998 ,79 :127 -132.
14. Maeng HY, Choi DK, Takeuchi M, et al . Appearance of osteopontin -expressing fibroblastic cells in early rat stomach carcinogenesis and stomach tumors induced with N-methyl-N'-nitro-N- nitro- soguanidine. Jpn J Cancer Res, 2002 ,93 :960 - 967.
15. Weber GF , Zawaideh S , Hikita S , et al . Phosphorylation macrophage migration and activation [J]. J Leukoc Biol ,2002 ,72(4) :752-761.
16. Rosen DG, Wang L, Atkinson YN, et al. Potential makers that complement expression of CA125 in epithelial ovarian cancer . Gynecol Oncol, 2005. 99: 267-277.
17. Maki M ,Hirota S,Kaneko Y, et al. Expression of osteopontin messenger RNA by macrophages in ovarian serous papillary cyst adenocarcinoma: a possible association with calcification of psammoma bodies . Pathol Int. 2000. 50: 531-535.
18. Fisher LW , Jain A, Taybeck M, et al. Small integrin binding ligand N-linked glycoprotein gene family expression in different cancers. Clin Cancer Res. 2004. 10: 8501-8511.
19. O'NeiU CJ. Deavers MT,Malpica A, et al. An immuno—histochemical comparison between low-grade and high-grade ovarian serous carcinomas : significantly higher expression of p53, MIB1, BCI2, HER-2/neu, and C—KIT in hjgh—grade neoplasms. Am J Surg Pathol, 2005, 29: 1034-1041.
20. Bellahene A , Cast ronovo C. Increased expression of osteonectin and osteopontin , two bone matrix proteins in human breast cancer [J] . Am J Pat hol ,1995 ,146 (1):95-100.
21. Hirota S , Ito A , Nagoshi J , et al . Expression of bone matrix protein messenger ribonucleic acids in human breast cancers. Possible involvement of osteopontin in development of calcifying foci [J] . Lab Invest ,1995 ,72 (1):64-69.
22. Tokes AM , Krausz J , Kulka J , et al. Role of osteopontin in the formation of microcalcifications in breast cancer [J]. Orv Hetil, 2002,143 (31) :1841-1846.
23.Yang G, Zhang XH , Zhang ZG, et al . Correlation of X-ray features in mammography and expression of OPN and ON of breast carcinoma[J] . J Clin Radiol,2006,25(2):134-137.
24.Rudland PS,Platt Higgins A,E1 Tanani M . et al. Prognostic significance of the metastasis associated protein osteopontin in human breast cancer[J]. Cancer Res, 2002. 1 5(1): 3417-3427.
25. Kim YW, Park YK, Lee J , et al. Expression of osteopontin and osteonectin in breast cancer [J]. J Korean Med ,1998 ,13 (6) :652-657.
26. Tuck AB , Chambers AF. The role of osteopontin in breast cancer : clinical and experimental studies. Mammary Gland Biol Neoplasia , 2001 ,6 : 419 - 429.
27. Le QT ,Sutphin PD ,Taychaudhuri S , et al. Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas[J]. Clin Cancer Res ,2003 ,9 (1) :59-67.
28. Petrik D ,Cao H ,Zhu Y, et al. An expanded study of the relationship between osteopontin ,tumor PO2 and prognosis in head and neck squamous cell carcinomas[J]. J Clin Oncol ,2005 ,23(16s) :5521.
29. Celetti A ,Testa D ,Staibano S , et al . Overexpression of the cytokine osteopontin identifies aggressive latyngesl squamous cell carcinomas and enhances carcinoma cell proliferation and invasiveness[J ] . Clin Cancer Res ,2005 ,11(22) :8019-8027.
30. Takano T ,Haseqawa Y,Matsuzuka F , et al . Gene expression profiles in thyroid carcinomas[J] .Br J Cancer ,2000,83(11) :1495-1502.
31. Guarino V ,Faviana P ,Salvatore G, et al . Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness [J]. J Clin Endocrinol Metab , 2005 , 90 (9): 5270-5278.
32. Ghulam M Tunio, Seiichi Hirota, Shintaro Nomura, et al .Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer. Arch Pathol Lab Med, 1998 Dec, 122 (12) :1087-1090.
33. Yeatman TJ ,Chambers AF. Osteopontin and colon cancer progression [J] . Clin Exp Metastasis ,2003 ,20(1) :85-90.
34. Guo H , Cai CO , Schroeder RA , et al. Osteopontin is a negative feed back regulator of nitric oxide synthesis in murine macrophages. J Immunol , 2001,166:1079-1086.
35. Bautista DS , Xuan JW, Hota C , et al . Inhibition of Arg-Gly-Asp (RGD)-mediated cell adhesion to osteopontin by a monoclonal antibody against osteopontin. Biol Chem, 1994 ,269 .23280 - 23285.
36. Hirama M, Takahashi F , Takahashi K, et al . Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth. Cancer Lett, 2003 ,198 :107 -117.
37. Overgaard J ,Eriksen JG,Nordsmark M, et al. Plasma osteopontin , hypoxia , and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer : results from the DAHANCA 5 randomised double-bind placcbo-controlled trial [J ]. Lancet Oncol ,2005 ,6 (10): 757-764.
38. Rudland PS , Platt-Higgins A , EI-Tanani M , et al. Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer [J ] . Cancer Res ,2002 ,15(1) :3417-3427.
39. Donati V , Boldrini L , Dell'Omodarme M, et al. Osteopontin expression and prognostic significance in non-small cell lung cancer. Clin Cancer Res , 2005,11 :6459-6465.
[1]Oldberg A,Franzen A,Heinegard D.Cloning and sequence analysis ofrat bone sialoprotein(osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence.Proc Natl Acad Sci USA,1986,83:8819-8823.
[2]Wai PY,Kuo PC.The role of osteopontin in tumor metastasis.J Surg Res,2004,121:228-241.
[3]贺斌,刘银坤,汤钊猷,等.肝癌中骨桥蛋白表达的临床意义.中华肝脏病杂志,1998,4:208-210.
[4]Rudland PS,Higgins AP,Tanani ME,et al.Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer.Cancer Res,2002,62:3417-3427.
[5]Ariztia EV,Subbarao V,Solt DB,et al.Osteopontin contributes to heaptocyte growth factor-induced tumor growth and metastasis formation.Exp Cell Res,2003,288:257-267.
[6]Ue T,Yolozaki H,Kitadai Y,et al.Co-expression of osteopontin and CD44v9 in gastric cancer.Int J Cancer,1998,79:127-132.
[7]Guarino V,Faviana P,Salvatore G,et al.Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness.J Clin Endocrinol Metab.2005 Sep;90(9):5270-5278.
[8]季正标,张晖,俞清,等.灰阶及彩色多普勒血流成像在甲状腺癌诊断中的应用.中国医学影像技术,2002,18(7):556-558.
[9]刘洪枫,唐伟松,杨志英.甲状腺钙化性病灶与甲状腺癌.中国医学科学院学报,2003,25(5):626-629.
[10]Khoo ML,Asa SL,Witterick IJ,et al.T hyroid calcification and its association with thyroid carcinoma.HeM Neck,2002,24(7):651-655.
[11]Kakkos SK,Scopa CD,Chalmoukis AK,et al.Relative risk of cancer in sonographically detected thyroid nodules with calcifications,J Clin Ultrasound,2000,28(7):347-352.
[12]Hirota S,Ito A,Nagoshi J,et al.Expression of bone matrix protein messenger rribonucleic acids in human breast cancers.Possible involvement of osteopontin in development of calcifying foci.Lab Invest.1995,Jan;72(1):64-69.
[13]Fluge φ,Bruland O,Akslen LA,et al.Possible re lation of osteopontin to development of psammoma bodies in human papillary thyroid cancer.Arch Pathol Lab Med.1998 Dec;122(12):1087-90.
1.Horak ER,Leek R, Klenk N , et al. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet, 1992, 340 (8828) : 1120-1124.
2.ToiM , Kashitani J , Tominaga T.Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma.Int J Cancer, 1993,55(3) :371-374.
3.Tomisaki S, Ohno S, Ichiyoshi Y, et al. Microvessel quantification and its possible relation with liver metastasis in colorectal cancer.Cancer, 1996, 77 (8): 1722-1728.
4.Ichinoe M, Mikami T, Shiraishi H, et al. High microvascular density is correlated with high VEGF, NOS and COX-2 expression in penetrating growth-type early gastric carcinomas [J]. Histopathology, 2004; 45 (6) : 612 - 618.
5.Weidner N. Intratumor microvessel density as a prognostic factor in cancer . Am J Pathol, 1995 ,147:9-19.
6.Weidner N , Folkman J , Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst, 1992, 84 (24): 1875-1887.
7.Raspollini MR, Amunni G, Villanucci A, et al. Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma [J]. Int J Gynecol Cancer, 2004; 14 (5) : 815-823.
8.Passe TJ ,Bluemke DA , Siegelman SS. Tumor angiogenesis : tutorial on implications for imaging. Radiology ,1997 ,203 .593-600.
9.Connolly DT , Heuvelman DM , Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest ,1989,84 :1470-1478.
10.Kirmaz C, Ozbilgin K, Yuksel H, et al. Increased expression of angiogenic markers in patients with seasonal allergic rhinitis [ J ]. Eur Cytokine Netw, 2004; 315 (4): 317-322.
11. Fina L, Molgaard H,Robertson D, etc. Expression of the CD_(34) gene in vascular endothelial cells. Blood, 1990,75(12):2417-2426.
12.Stabenow E, Tavares MR, Ab'Saber AM,et al. Angiogenesis as an indicator of metastatic potential in papillary thyroid carcinoma. Clinics. 2005 Jun;60(3):233-40.
13.Akslen LA, Livolsi VA.Increased angiogenesis in papillary thyroid carcinoma but lack of prognostic importance.Hum Pathol. 2000 Apr;31(4):439-442.
14.Todd D ,Brian J ,David A ,et al . Evaluation of palpable breast masses with color Doppler sonography and gray scale imaging. J Ultrasound Med , 1998,17:110-111.
15.Clark KJ,Cronan JJ,Scola FH.Color Doppler sonography autonomic and physiologic assessment of the thyroid.J Clin Ultrasound. 1995;23:215-223.
16.Folkman J , Shing Y.Angiogenesis.J Biol, 1992, 267: 603-606.
17.Jebreel A, England J, Bedford K,et al. Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseases.Int J Exp Pathol. 2007 Aug;88(4):271-277.