CD147和D2-40在宫颈鳞癌中的表达及意义
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摘要
目的：研究细胞外基质金属蛋白酶诱导因子(CD147, EMMPRIN)与D2-40标记的微淋巴管密度(MLVD)在宫颈病变中的表达。探讨CD147、D2-40标记的微淋巴管密度(MLVD)与宫颈病变的关系、在宫颈鳞癌中与各临床病理指标之间的关系以及预测宫颈鳞癌淋巴转移的价值。
方法：选取89例宫颈病变石蜡标本,其中包括11例正常宫颈组织、15例CIN组织、63例宫颈鳞癌组织。宫颈鳞癌中,病理未发现淋巴结转移者34例,发现淋巴结转移者29例。宫颈鳞癌按FIGO分期(2000年)：Ⅰa2期2例,Ⅰb1期26例,Ⅰb2期8例,Ⅱa期25例,Ⅱb早期2例。病理分化程度：高分化6例,中分化32例,低分化25例。浸润深度：浸润浅肌层22例,浸润中肌层5例,浸润深肌层36例。标本运用兔抗人CD147单克隆抗体、小鼠抗人D2-40单克隆抗体,采用免疫组织化学技术(PV二步法),经DAB染色后均在光镜下观察CD147的表达以及计数D2-40标记的微淋巴管密度(MLVD)。应用SPSS17.0统计软件对相关数据进行统计学分析。
结果：
1.CD147的阳性率在正常宫颈组、CIN组、宫颈鳞癌组逐渐增高,分别为9.1%(1/11)、66.7%(10/15)、93.7%(59/63),三组间比较差异有统计学意义(P=0.000)。宫颈鳞癌高分化、低-中分化组织中CD147高表达率分别为16.7%(1/6),71.9%(41/57),两组间差有统计学意义(P<0.05)。宫颈鳞癌无淋巴结转移、有淋巴转移组织中CD147的高表达率分别为50.0%(17/34)、86.2%(25/29),两组间比较差异有统计学意义(P<0.05)。宫颈鳞癌中,CD147的高表达率与年龄、临床分期、肿块最大直径、浸润深度和癌栓无关(P>0.05)。
2.D2-40标记的微淋巴管密度(MLVD)在正常宫颈组、CIN组、宫颈鳞癌组分别为1.55±1.04、7.40±2.87、17.33±5.57,三组间比较差异有统计学意义(P<0.05)。宫颈鳞癌高分化、低-中分化组织中D2-40标记的微淋巴管密度(MLVD)分别为12.17±2.99、17.88±5.52,两组间比较差异有统计学意义(P<0.05)。宫颈鳞癌浸润≤2/3肌层、>2/3肌层组织中D2-40标记的微淋巴管密度(MLVD)分别为15.56±5.68、18.67±5.18,两组间比较差异有统计学意义(P<0.05)。宫颈鳞癌无淋巴结转移、有淋巴结转移组织中D2-40标记的微淋巴管密度(MLVD)分别为14.12±4.90、21.10±3.63,两组间比较差异有统计学意义(P<0.05)。宫颈鳞癌中,D2-40标记的微淋巴管密度(MLVD)与年龄、临床分期、肿块最大直径和癌栓无关(P>0.05)。
3.所有89例宫颈组织中CD147的表达与D2-40标记的微淋巴管密度(MLVD)呈正相关,rs=0.794(P=0.000)。宫颈鳞癌中检测CD147的表达及D2-40标记的微淋巴管密度(MLVD)对预测淋巴转移均有一定的价值(CD147的ROC曲线下面积为0.749,灵敏度为58.6%,特异度为79.4%；D2-40标记的MLVD的ROC曲线下面积为0.872,灵敏度为75.9%,特异度为79.4%),联合检测价值更大(ROC曲线下面积为0.877,灵敏度为82.8%,特异度为82.4%)。
结论：
1.CD147的阳性率在正常宫颈、CIN及宫颈鳞癌组织中逐渐增高,且其高表达率与宫颈鳞癌淋巴转移以及分化程度有关,提示CD147可能参与宫颈鳞癌的发生、发展及淋巴转移。
2.D2-40标记的微淋巴管密度(MLVD)在宫颈鳞癌中明显高于正常宫颈组织及CIN组织,且与宫颈鳞癌的分化程度、浸润深度及淋巴转移有关。提示微淋巴管形成与宫颈鳞癌的进展有关。
3.在宫颈组织中CD147的表达与D2-40标记的微淋巴管密度(MLVD)呈正相关。宫颈鳞癌中检测CD147的表达及D2-40标记的微淋巴管密度(MLVD)对预测淋巴转移均有一定的价值,联合检测价值更大。
Objective
To detect the expression of Extracellular Matrix Metalloproteinase Inducer (CD147) and micro-lymphatic vessel density(MLVD) which markered by D2-40 in cervical tissue. To discuss their relationship between CD147, MLVD which markered by D2-40 and clinicopathology parameters in cervical squamous cell carcinoma. To determine the value in prognosticating lymph node metastasis of cervical squamous cell carcinoma.
Methods
89 cases of cervical tissue were collected, including 11 cases of normal cervical tissue,15 cases of CIN and 63 cases of cervical squamous cell carcinoma. In cervical squamous cell carcinoma, pathological lymph node metastasis was not found in 34 cases and found in 29 cases. Cervical squamous cell carcinoma included 2 cases ofⅠa2 stage,26 cases ofⅠb1 stage,8 cases ofⅠb2 stage,25 cases ofⅡa stage and 2 cases ofⅡb-early stage according to FIGO(2000). Cervical squamous cell carcinoma also included 6 cases of well differentiated tissue,32 cases of moderately differentiated tissue and 25 cases of poorly differentiated tissue according to pathological degree of differentiation, 22 cases of invading superficial myometrium,5 cases of invading middle myometrium and 36 cases of invading deep myometrium according to depth of invasion. With anti-rabbit CD147 monoclonal antibody, anti-mouse D2-40 monoclonal antibody, all samples were underwent immunohistochemistry technique (PV two-step method) by DAB staining. Then we observed their expression of CD147 and MLVD which markered by D2-40 under light microscope and analyzed the data by statistical software SPSS 17.0.
Results
1. In normal uterine cervical tissue, CIN and cervical squamous cell carcinoma, the positive rates of CD147 were 9.1%(1/11),66.7%(10/15) and 93.7%(59/63), gradually increased, the difference among the three groups was statistically significant (P=0.000). In cervical squamous cell carcinoma, the high expression rates of CD147 in well differentiated tissue, poorly-moderately differentiated tissue were 16.7%(1/6) and 71.9%(41/57), the difference between the two groups was statistically significant(P<0.05). The high expression rates of CD147 in cervical squamous cell carcinoma tissue without lymph node metastasis and with lymph node metastasis were 50.0%(17/34) and 86.2%(25/29), the difference between the two groups was statistically significant(P<0.05). In cervical squamous cell carcinoma, the high expression rates of CD147 had no correlation with age, clinical stage, tumor diameter, depth of invasion and embolus (P>0.05).
2. In normal uterine cervical tissue, CIN and cervical squamous cell carcinoma, MLVD markered by D2-40 was 1.55±1.04,7.40±2.87 and 17.33±5.57, the difference among the three groups was statistically significant(P<0.05). In cervical squamous cell carcinoma, MLVD markered by D2-40 in well differentiated tissue and poorly-moderately differentiated tissue were 12.17±2.99 and 17.88±5.52, the difference between the two groups was statistically significant(P<0.05). In cervical squamous cell carcinoma, MLVD markered by D2-40 in invasion of myometrium≤2/3 and >2/3 was 15.56±5.68 and 18.67±5.18, the difference between the two groups was statistically significant (P<0.05). MLVD markered by D2-40 in cervical squamous cell carcinoma without lymph node metastasis and with lymph node metastasis were 14.12±4.90 and 21.10±3.63, the difference between the two groups was statistically significant (P<0.05). In cervical squamous cell carcinoma, MLVD which markered by D2-40 had no correlation with age, clinical stage, tumor diameter and embolus (P>0.05).
3. In all cases of cervical tissue, the expression of CD147 and MLVD which markered by D2-40 were correlated positively (rs =0.794,P=0.000). In cervical squamous cell carcinoma, detecting the expression of CD147 and MLVD which markered by D2-40 may prognosticated lymph node metastasis(the area under ROC curve, sensitivity, specificity of CD147 and MLVD which markered by D2-40 were 0.749,58.6%,79.4% and 0.872,75.9%,79.4%). Detecting both of them was more valuable (the area under ROC curve, sensitivity, specificity of their combination were 0.877,82.8% and 82.4%).
Conclusion
1. The positive rate of CD147 gradually increased in normal uterine cervical tissue, CIN and cervical squamous cell carcinoma. The high expression rates of CD147 in cervical squamous cell carcinoma was significantly higher than normal cervical tissue and CIN, and the high expression rates of CD147 in cervical squamous cell carcinoma was in connection with lymph node metastasis and pathological degree of differentiation. CD147 may be involved in the development and metastasis of cervical squamous cell carcinoma.
2. MLVD markered by D2-40 in cervical squamous cell carcinoma was significantly higher than normal cervical tissue and CIN, and in cervical squamous cell carcinoma it was in connection with depth of invasion, pathological degree of differentiation and lymph node metastasis. Micro-lymphatic vessel may be involved in the progress of cervical squamous cell carcinoma.
3. In cervical tissue, the expression of CD147 and MLVD which markered by D2-40 were positively correlated. In cervical squamous cell carcinoma, detecting the expression of CD147 and MLVD which markered by D2-40 may prognosticated lymph node metastasis, and detecting both of them was more valuable.
方法：选取89例宫颈病变石蜡标本,其中包括11例正常宫颈组织、15例CIN组织、63例宫颈鳞癌组织。宫颈鳞癌中,病理未发现淋巴结转移者34例,发现淋巴结转移者29例。宫颈鳞癌按FIGO分期(2000年)：Ⅰa2期2例,Ⅰb1期26例,Ⅰb2期8例,Ⅱa期25例,Ⅱb早期2例。病理分化程度：高分化6例,中分化32例,低分化25例。浸润深度：浸润浅肌层22例,浸润中肌层5例,浸润深肌层36例。标本运用兔抗人CD147单克隆抗体、小鼠抗人D2-40单克隆抗体,采用免疫组织化学技术(PV二步法),经DAB染色后均在光镜下观察CD147的表达以及计数D2-40标记的微淋巴管密度(MLVD)。应用SPSS17.0统计软件对相关数据进行统计学分析。
结果：
1.CD147的阳性率在正常宫颈组、CIN组、宫颈鳞癌组逐渐增高,分别为9.1%(1/11)、66.7%(10/15)、93.7%(59/63),三组间比较差异有统计学意义(P=0.000)。宫颈鳞癌高分化、低-中分化组织中CD147高表达率分别为16.7%(1/6),71.9%(41/57),两组间差有统计学意义(P<0.05)。宫颈鳞癌无淋巴结转移、有淋巴转移组织中CD147的高表达率分别为50.0%(17/34)、86.2%(25/29),两组间比较差异有统计学意义(P<0.05)。宫颈鳞癌中,CD147的高表达率与年龄、临床分期、肿块最大直径、浸润深度和癌栓无关(P>0.05)。
2.D2-40标记的微淋巴管密度(MLVD)在正常宫颈组、CIN组、宫颈鳞癌组分别为1.55±1.04、7.40±2.87、17.33±5.57,三组间比较差异有统计学意义(P<0.05)。宫颈鳞癌高分化、低-中分化组织中D2-40标记的微淋巴管密度(MLVD)分别为12.17±2.99、17.88±5.52,两组间比较差异有统计学意义(P<0.05)。宫颈鳞癌浸润≤2/3肌层、>2/3肌层组织中D2-40标记的微淋巴管密度(MLVD)分别为15.56±5.68、18.67±5.18,两组间比较差异有统计学意义(P<0.05)。宫颈鳞癌无淋巴结转移、有淋巴结转移组织中D2-40标记的微淋巴管密度(MLVD)分别为14.12±4.90、21.10±3.63,两组间比较差异有统计学意义(P<0.05)。宫颈鳞癌中,D2-40标记的微淋巴管密度(MLVD)与年龄、临床分期、肿块最大直径和癌栓无关(P>0.05)。
3.所有89例宫颈组织中CD147的表达与D2-40标记的微淋巴管密度(MLVD)呈正相关,rs=0.794(P=0.000)。宫颈鳞癌中检测CD147的表达及D2-40标记的微淋巴管密度(MLVD)对预测淋巴转移均有一定的价值(CD147的ROC曲线下面积为0.749,灵敏度为58.6%,特异度为79.4%；D2-40标记的MLVD的ROC曲线下面积为0.872,灵敏度为75.9%,特异度为79.4%),联合检测价值更大(ROC曲线下面积为0.877,灵敏度为82.8%,特异度为82.4%)。
结论：
1.CD147的阳性率在正常宫颈、CIN及宫颈鳞癌组织中逐渐增高,且其高表达率与宫颈鳞癌淋巴转移以及分化程度有关,提示CD147可能参与宫颈鳞癌的发生、发展及淋巴转移。
2.D2-40标记的微淋巴管密度(MLVD)在宫颈鳞癌中明显高于正常宫颈组织及CIN组织,且与宫颈鳞癌的分化程度、浸润深度及淋巴转移有关。提示微淋巴管形成与宫颈鳞癌的进展有关。
3.在宫颈组织中CD147的表达与D2-40标记的微淋巴管密度(MLVD)呈正相关。宫颈鳞癌中检测CD147的表达及D2-40标记的微淋巴管密度(MLVD)对预测淋巴转移均有一定的价值,联合检测价值更大。
Objective
To detect the expression of Extracellular Matrix Metalloproteinase Inducer (CD147) and micro-lymphatic vessel density(MLVD) which markered by D2-40 in cervical tissue. To discuss their relationship between CD147, MLVD which markered by D2-40 and clinicopathology parameters in cervical squamous cell carcinoma. To determine the value in prognosticating lymph node metastasis of cervical squamous cell carcinoma.
Methods
89 cases of cervical tissue were collected, including 11 cases of normal cervical tissue,15 cases of CIN and 63 cases of cervical squamous cell carcinoma. In cervical squamous cell carcinoma, pathological lymph node metastasis was not found in 34 cases and found in 29 cases. Cervical squamous cell carcinoma included 2 cases ofⅠa2 stage,26 cases ofⅠb1 stage,8 cases ofⅠb2 stage,25 cases ofⅡa stage and 2 cases ofⅡb-early stage according to FIGO(2000). Cervical squamous cell carcinoma also included 6 cases of well differentiated tissue,32 cases of moderately differentiated tissue and 25 cases of poorly differentiated tissue according to pathological degree of differentiation, 22 cases of invading superficial myometrium,5 cases of invading middle myometrium and 36 cases of invading deep myometrium according to depth of invasion. With anti-rabbit CD147 monoclonal antibody, anti-mouse D2-40 monoclonal antibody, all samples were underwent immunohistochemistry technique (PV two-step method) by DAB staining. Then we observed their expression of CD147 and MLVD which markered by D2-40 under light microscope and analyzed the data by statistical software SPSS 17.0.
Results
1. In normal uterine cervical tissue, CIN and cervical squamous cell carcinoma, the positive rates of CD147 were 9.1%(1/11),66.7%(10/15) and 93.7%(59/63), gradually increased, the difference among the three groups was statistically significant (P=0.000). In cervical squamous cell carcinoma, the high expression rates of CD147 in well differentiated tissue, poorly-moderately differentiated tissue were 16.7%(1/6) and 71.9%(41/57), the difference between the two groups was statistically significant(P<0.05). The high expression rates of CD147 in cervical squamous cell carcinoma tissue without lymph node metastasis and with lymph node metastasis were 50.0%(17/34) and 86.2%(25/29), the difference between the two groups was statistically significant(P<0.05). In cervical squamous cell carcinoma, the high expression rates of CD147 had no correlation with age, clinical stage, tumor diameter, depth of invasion and embolus (P>0.05).
2. In normal uterine cervical tissue, CIN and cervical squamous cell carcinoma, MLVD markered by D2-40 was 1.55±1.04,7.40±2.87 and 17.33±5.57, the difference among the three groups was statistically significant(P<0.05). In cervical squamous cell carcinoma, MLVD markered by D2-40 in well differentiated tissue and poorly-moderately differentiated tissue were 12.17±2.99 and 17.88±5.52, the difference between the two groups was statistically significant(P<0.05). In cervical squamous cell carcinoma, MLVD markered by D2-40 in invasion of myometrium≤2/3 and >2/3 was 15.56±5.68 and 18.67±5.18, the difference between the two groups was statistically significant (P<0.05). MLVD markered by D2-40 in cervical squamous cell carcinoma without lymph node metastasis and with lymph node metastasis were 14.12±4.90 and 21.10±3.63, the difference between the two groups was statistically significant (P<0.05). In cervical squamous cell carcinoma, MLVD which markered by D2-40 had no correlation with age, clinical stage, tumor diameter and embolus (P>0.05).
3. In all cases of cervical tissue, the expression of CD147 and MLVD which markered by D2-40 were correlated positively (rs =0.794,P=0.000). In cervical squamous cell carcinoma, detecting the expression of CD147 and MLVD which markered by D2-40 may prognosticated lymph node metastasis(the area under ROC curve, sensitivity, specificity of CD147 and MLVD which markered by D2-40 were 0.749,58.6%,79.4% and 0.872,75.9%,79.4%). Detecting both of them was more valuable (the area under ROC curve, sensitivity, specificity of their combination were 0.877,82.8% and 82.4%).
Conclusion
1. The positive rate of CD147 gradually increased in normal uterine cervical tissue, CIN and cervical squamous cell carcinoma. The high expression rates of CD147 in cervical squamous cell carcinoma was significantly higher than normal cervical tissue and CIN, and the high expression rates of CD147 in cervical squamous cell carcinoma was in connection with lymph node metastasis and pathological degree of differentiation. CD147 may be involved in the development and metastasis of cervical squamous cell carcinoma.
2. MLVD markered by D2-40 in cervical squamous cell carcinoma was significantly higher than normal cervical tissue and CIN, and in cervical squamous cell carcinoma it was in connection with depth of invasion, pathological degree of differentiation and lymph node metastasis. Micro-lymphatic vessel may be involved in the progress of cervical squamous cell carcinoma.
3. In cervical tissue, the expression of CD147 and MLVD which markered by D2-40 were positively correlated. In cervical squamous cell carcinoma, detecting the expression of CD147 and MLVD which markered by D2-40 may prognosticated lymph node metastasis, and detecting both of them was more valuable.
引文
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[31]Karpanen T, Egeblad M, Karkkainen MJ, et al. Vascular endothelial growth factor C promotes tumor lymphanglogenesis and intralymphatic tumor growth. Cancer Res,2001,61(5):1786-1790.
[32]Sier CF, Zuidwijk K, Zijlmans HJ, et al. EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma. Int J Cancer,2006, 118 (12):2991-2998.
[33]Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40. Hum Pathol,2006, 37(9):1193-1199.
[34]Takanami I. Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non-small cell lung cancer.Oncol Rep,2006,15(2):437-442.
[35]Adachi Y, Nakamura H, Kitamura Y, et al. Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases. Pathol Int.2007,57(4):171-177.
[36]Miyahara M, Tanuma J, Sugihara K, et al. Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma. Cancer.2007,110(6):1287-1294.
[37]Chang LK, Garcia-Cardena G, Farnebo F, et al. Dose-dependent response of FGF-2 for lymphangiogenesis. Proc Natl Acad Sci U S A,2004,101(32):11658-11663.
[38]Padera TP, Kadambi A,di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science,2002,296(5574):1883-1886.
[39]谢晓冬,屈淑贤,郑振冻,等.人乳腺癌组织中D2-40标记的微淋巴管密度与血管内皮生长因子C表达的关系.中华肿瘤杂志,2008,30(5)：356-360.
[40]Arnaout-Alkarain A, Kahn HJ, Narod SA, et al. Significance of lymph vessel invasion identified by the endothelial lymphatic marker D2-40 in node negative breast cancer. Mod Pathol.2007,20(2):183-191.
[41]Arigami T, Natsugoe S, Uenosono Y, et al. Lymphatic invasion using D2-40 monoclonal antibody and its relationship to lymph node micrometastasis in pNO gastric cancer. Br J Cancer.2005,93(6):688-693.
[42]Niakosari F, Kahn HJ, Marks A, et al. Detection of lymphatic invasion in primary melanoma with monoclonal antibody D2-40:a new selective immunohistochemical marker of lymphatic endothelium. Arch Dermatol.2005, 141(4):440-444.
[43]Bordador LC, Li X, Toole B, et al. Expression of emmprin by oral squamous cell carcinoma. Int J Cancer,2000,85(3):347-352.
[44]Tsung AJ, Kargiotis O, Chetty C, et al. Downregulation of matrix metalloproteinase-2(MMP-2) utilizing adenovirus-mediated transfer of small interifring RNA(siRNA) in a novel spinal metastatic melanoma model. Int J Oncol, 2008,32(3):557-564.
[1]Olszewski WL. The lymphatic system in body homeostasis:physiological conditions. Lymphat Res Biol,2003,1(1):11-21.
[2]Witte MH, Jone K, Wilting J, et al. Structure function relationships in the lymphatic system and implications for cancer biology. Cancer Metastasis Rev,2006,25(2):159-184.
[3]Leu AJ, Berk DA, Lymboussaki A, et al. Absence of functional lymphatics within a murine sarcoma:a molecular and functional evaluation. Cancer Res,2000,60(16):4324-4327.
[4]Vleugel MM, Bos R, van der Groep P, et al. Lack of lymphangiogenesis during breast carcinogenesis. J Clin Pathol,2004,57(7):746-751.
[5]Padera TP, Kadambi A,di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics.Science,2002,296(5574):1883-1886.
[6]Cursiefen C, Chen L, Dana MR, et al. Corneal lymphangiogenesis:evidence, mechanisms, and implications for corneal transplant immunology. Cornea,2003, 22(3):273-281.
[7]Mouta Carreira C, Nasser SM,di Tomaso E, et al. LYVE-1 is not restricted to the lymph vessels:expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer Res,2001,61(22):8079-8084.
[8]傅仲学,肖世尧,王春毅,等.转录因子Prox-1对大肠癌中淋巴管生成的作用.中华消化外科杂志,2007,6(6)：455-458.
[9]Pepper MS, Tille JC, Nisato R, et al. Lymphangiogenesis and tumor metastasis.Cell Tissue Res,2003,314(1):167-177.
[10]Partanen TA, Arola J, Saaristo LA, et al. VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor,VEGFR-3,in fenestrated blood vessels in human tissue. FASEB J,2000,14(13):2087-2096.
[11]Cassella M, Skobe M. Lymphatics vessel activation in cancer. Ann N Y Acad Sci,2002,979:120-130.
[12]Schacht V, Dadras SS, Johnson LA, et al. Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. Am J Pathol,2005,166(3):913-921.
[13]Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40. Hum Pathol,2006, 37(9):1193-1199.
[14]Takanami I. Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non-small cell lung cancer. Oncol Rep,2006,15(2):437-442.
[15]Saad RS, Kordunsky L, Liu YL, et al. Lymphatic microvessel density as prognostic marker in colorectal cancer. Mod Pathol,2006,19(10):1317-1323.
[16]Gombos Z, Xu X, Chu CS, et al. Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early-stage squamous cell carcinoma of the uterine cervix. Clin Cancer Res,2005,11(23):8364-8371.
[17]Longatto-Filho A, Pinheiro C, Pereira SM, et al. Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix. Gynecol Oncol,2007,107(1):45-51.
[18]Van Trappen PO, Steele D, Lowe DG, et al. Expression of vascular endothelial growth factor(VEGF)-C and VEGF-D, and their receptor VEGFR-3,during different stages of cervical carcinogenesis. J Pathol,2003,201(4): 544-554.
[19]Stacker SA, Caesar C, Baldwin ME, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nature Med,2001,7(2):186-191.
[20]Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis.Nat Med, 2001,7(2):192-198.
[21]Mandriota SJ, Jussila L, Jeltsch M, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumor metastasis. EMBO J,2001, 20(4):672-682.
[22]Hirakawa S, Brown LF, Kodama S, et al. VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood,2007,109(3):1010-1017.
[23]Shida A, Fujioka S, Kobayashi K, et al. Expression of vascular endothelial growth factor (VEGF)-C and-D in gastric carcinoma. Int J Clin Oncol,2006,11(1):38-43.
[24]郭琳,张丹丹,王强.胃癌组织中VEGF-C及其受体的表达与淋巴结转移的关系.中国现代医学杂志,2007,17(6)：669-672.
[25]Wang LL, Yao GY, Zhang BY,et al. Expression and significance of CD 147 and E-cadherin in human gastric carcinoma. Zhonghua Zhong Liu Za Zhi,2009,31(7): 515-519.
[26]Yang JM, Xu Z, Wu H, et al. Overexpression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells. Mol Cancer Res,2003, 1(6):420-427.
[27]Rosenthal EL, Zhang W, Talbert M, et al. Extracellular matrix metalloprotease inducer-expressing head and neck squamous cell carcinoma cells promote fibroblast-mediated type Ⅰ collagen degradation in vitro. Mol Cancer Res, 2005,3(4):195-202.
[28]Tang Y, Kesavan P, Nakada MT, et al. Tumor-stroma interaction:positive feedback regulation of extracellular matrix metalloproteinase inducer(EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res,2004,2(2):73-80.
[29]Kanekura T, Chen X, Kanzaki T. Basigin (CD 147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer,2002,99(4):520-528.
[30]蒋建利,姚西英,周筠,等.HAb18G/CD147刺激人肝癌细胞分泌基质金属蛋白酶的机制探讨.肿瘤,2004,24(6)：534-537.
[31]Yang JM, O'Neill P, Jin W, et al. Extracellular matrix metalloproteinase inducer (CD 147) confers resistance of breast cancer cells to Anoikis through inhibition of Bim. J Biol Chem,2006,281(14):9719-9727.
[32]He XW, Yu X, Liu T, et al. Vector-based RNA interference against vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of colorectal cancer in vivo in mice. Chin Med J.2008,121(5):439-444.
[33]Bo C, Xiaopeng D, Chuanliang P, et al. Expression of vascular endothelial growth factors C and D correlates with lymphangiogenesis and lymph node metastasis in lung adenocarcinoma. Thorac Cardiovasc Surg.2009,57(5):291-294.
[34]Liu Y, Ji R, Li J,et al. Correlation effect of EGFR and CXCR4 and CCR7 chemokine receptors in predicting breast cancer metastasis and prognosis. J Exp Clin Cancer Res.2010,29:16.
[35]Gerli R, Ibba L, Fruschelli C. Ultrastructural cytochemistry of anchoring filaments of human lymphatic capillaries and their relation to elastic fibers. Lymphology,1991,24(3):105-112.
[36]Sako A, Kitayama J, Ishikawa M, et al. Impact of immunohistochemically identified lymphatic invasion on nodal metastasis in early gastric cancer. Gastric Cancer,2006,9(4):295-302.
[37]Nakamura Y, Yasuoka H, Tsujimoto M, et al. Importance of lymph vessels in gastric cancer:a prognostic indicator in general and a predictor for lymph node matastasis in early stage cancer. J Clin Pathol,2006,59(1):77-82.
[38]Joukov V, Pajusola K, Kaipainen A, et al. A novel vascular endothelial growth factor, VEGF-C,is a ligand for the Flt4(VEGFR-3) and KDR(VEGFR-2) receptor tyrosine kinases. EMBO J,1996,15(2):290-298.
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[5]Tang Y, Kesavan P, Nakada MT, et al. Tumor-stroma interaction:positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res,2004 (2):73-80.
[6]蒋建利,姚西英,周筠,等.HAb18G/CD147刺激人肝癌细胞分泌基质金属蛋白酶的机制探讨.肿瘤,2004,24(6):534-537.
[7]Yang JM, O'Neill P, Jin W, et al. Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to Anoikis through inhibition of Bim. J Biol Chem,2006,281 (14):9719-9727.
[8]Kanekura T, Chen X, Kanzaki T. Basigin(CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer,2002,99(4):520-528.
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[20]Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi's sarcoma and a subset of angiosarcomas. Mod Pathol,2002,15(4):434-440.
[21]Saad RS, Kordunsky L, Liu YL, et al. Lymphatic microvessel density as prognostic marker in colorectal cancer. Mod Pathol,2006,19 (10):1317-1323.
[22]Gombos Z, Xu X, Chu CS, et al. Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early-stage squamous cell carcinoma of the uterine cervix. Clin Cancer Res,2005,11(23):8364-8371.
[23]Van der Auwera I, Van den Eynden GG, Colpaert CG, et al. Tumor lymphangiogenesis in inflammatory breast carcinoma:a histomorphometric study. Clin Cancer Res,2005,11(21):7637-7642.
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[29]Yu W, Liu J, Xiong X,et al. Expression of MMP9 and CD 147 in invasive squamous cell carcinoma of the uterine cervix and their implication. Pathol Res Pract. 2009,205(10):709-715.
[30]Wang LL, Yao GY, Zhang BY,et al. Expression and significance of CD147 and E-cadherin in human gastric carcinoma. Zhonghua Zhong Liu Za Zhi,2009,31(7): 515-519.
[31]Karpanen T, Egeblad M, Karkkainen MJ, et al. Vascular endothelial growth factor C promotes tumor lymphanglogenesis and intralymphatic tumor growth. Cancer Res,2001,61(5):1786-1790.
[32]Sier CF, Zuidwijk K, Zijlmans HJ, et al. EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma. Int J Cancer,2006, 118 (12):2991-2998.
[33]Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40. Hum Pathol,2006, 37(9):1193-1199.
[34]Takanami I. Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non-small cell lung cancer.Oncol Rep,2006,15(2):437-442.
[35]Adachi Y, Nakamura H, Kitamura Y, et al. Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases. Pathol Int.2007,57(4):171-177.
[36]Miyahara M, Tanuma J, Sugihara K, et al. Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma. Cancer.2007,110(6):1287-1294.
[37]Chang LK, Garcia-Cardena G, Farnebo F, et al. Dose-dependent response of FGF-2 for lymphangiogenesis. Proc Natl Acad Sci U S A,2004,101(32):11658-11663.
[38]Padera TP, Kadambi A,di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science,2002,296(5574):1883-1886.
[39]谢晓冬,屈淑贤,郑振冻,等.人乳腺癌组织中D2-40标记的微淋巴管密度与血管内皮生长因子C表达的关系.中华肿瘤杂志,2008,30(5)：356-360.
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[41]Arigami T, Natsugoe S, Uenosono Y, et al. Lymphatic invasion using D2-40 monoclonal antibody and its relationship to lymph node micrometastasis in pNO gastric cancer. Br J Cancer.2005,93(6):688-693.
[42]Niakosari F, Kahn HJ, Marks A, et al. Detection of lymphatic invasion in primary melanoma with monoclonal antibody D2-40:a new selective immunohistochemical marker of lymphatic endothelium. Arch Dermatol.2005, 141(4):440-444.
[43]Bordador LC, Li X, Toole B, et al. Expression of emmprin by oral squamous cell carcinoma. Int J Cancer,2000,85(3):347-352.
[44]Tsung AJ, Kargiotis O, Chetty C, et al. Downregulation of matrix metalloproteinase-2(MMP-2) utilizing adenovirus-mediated transfer of small interifring RNA(siRNA) in a novel spinal metastatic melanoma model. Int J Oncol, 2008,32(3):557-564.
[1]Olszewski WL. The lymphatic system in body homeostasis:physiological conditions. Lymphat Res Biol,2003,1(1):11-21.
[2]Witte MH, Jone K, Wilting J, et al. Structure function relationships in the lymphatic system and implications for cancer biology. Cancer Metastasis Rev,2006,25(2):159-184.
[3]Leu AJ, Berk DA, Lymboussaki A, et al. Absence of functional lymphatics within a murine sarcoma:a molecular and functional evaluation. Cancer Res,2000,60(16):4324-4327.
[4]Vleugel MM, Bos R, van der Groep P, et al. Lack of lymphangiogenesis during breast carcinogenesis. J Clin Pathol,2004,57(7):746-751.
[5]Padera TP, Kadambi A,di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics.Science,2002,296(5574):1883-1886.
[6]Cursiefen C, Chen L, Dana MR, et al. Corneal lymphangiogenesis:evidence, mechanisms, and implications for corneal transplant immunology. Cornea,2003, 22(3):273-281.
[7]Mouta Carreira C, Nasser SM,di Tomaso E, et al. LYVE-1 is not restricted to the lymph vessels:expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer Res,2001,61(22):8079-8084.
[8]傅仲学,肖世尧,王春毅,等.转录因子Prox-1对大肠癌中淋巴管生成的作用.中华消化外科杂志,2007,6(6)：455-458.
[9]Pepper MS, Tille JC, Nisato R, et al. Lymphangiogenesis and tumor metastasis.Cell Tissue Res,2003,314(1):167-177.
[10]Partanen TA, Arola J, Saaristo LA, et al. VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor,VEGFR-3,in fenestrated blood vessels in human tissue. FASEB J,2000,14(13):2087-2096.
[11]Cassella M, Skobe M. Lymphatics vessel activation in cancer. Ann N Y Acad Sci,2002,979:120-130.
[12]Schacht V, Dadras SS, Johnson LA, et al. Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. Am J Pathol,2005,166(3):913-921.
[13]Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40. Hum Pathol,2006, 37(9):1193-1199.
[14]Takanami I. Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non-small cell lung cancer. Oncol Rep,2006,15(2):437-442.
[15]Saad RS, Kordunsky L, Liu YL, et al. Lymphatic microvessel density as prognostic marker in colorectal cancer. Mod Pathol,2006,19(10):1317-1323.
[16]Gombos Z, Xu X, Chu CS, et al. Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early-stage squamous cell carcinoma of the uterine cervix. Clin Cancer Res,2005,11(23):8364-8371.
[17]Longatto-Filho A, Pinheiro C, Pereira SM, et al. Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix. Gynecol Oncol,2007,107(1):45-51.
[18]Van Trappen PO, Steele D, Lowe DG, et al. Expression of vascular endothelial growth factor(VEGF)-C and VEGF-D, and their receptor VEGFR-3,during different stages of cervical carcinogenesis. J Pathol,2003,201(4): 544-554.
[19]Stacker SA, Caesar C, Baldwin ME, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nature Med,2001,7(2):186-191.
[20]Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis.Nat Med, 2001,7(2):192-198.
[21]Mandriota SJ, Jussila L, Jeltsch M, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumor metastasis. EMBO J,2001, 20(4):672-682.
[22]Hirakawa S, Brown LF, Kodama S, et al. VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood,2007,109(3):1010-1017.
[23]Shida A, Fujioka S, Kobayashi K, et al. Expression of vascular endothelial growth factor (VEGF)-C and-D in gastric carcinoma. Int J Clin Oncol,2006,11(1):38-43.
[24]郭琳,张丹丹,王强.胃癌组织中VEGF-C及其受体的表达与淋巴结转移的关系.中国现代医学杂志,2007,17(6)：669-672.
[25]Wang LL, Yao GY, Zhang BY,et al. Expression and significance of CD 147 and E-cadherin in human gastric carcinoma. Zhonghua Zhong Liu Za Zhi,2009,31(7): 515-519.
[26]Yang JM, Xu Z, Wu H, et al. Overexpression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells. Mol Cancer Res,2003, 1(6):420-427.
[27]Rosenthal EL, Zhang W, Talbert M, et al. Extracellular matrix metalloprotease inducer-expressing head and neck squamous cell carcinoma cells promote fibroblast-mediated type Ⅰ collagen degradation in vitro. Mol Cancer Res, 2005,3(4):195-202.
[28]Tang Y, Kesavan P, Nakada MT, et al. Tumor-stroma interaction:positive feedback regulation of extracellular matrix metalloproteinase inducer(EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res,2004,2(2):73-80.
[29]Kanekura T, Chen X, Kanzaki T. Basigin (CD 147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer,2002,99(4):520-528.
[30]蒋建利,姚西英,周筠,等.HAb18G/CD147刺激人肝癌细胞分泌基质金属蛋白酶的机制探讨.肿瘤,2004,24(6)：534-537.
[31]Yang JM, O'Neill P, Jin W, et al. Extracellular matrix metalloproteinase inducer (CD 147) confers resistance of breast cancer cells to Anoikis through inhibition of Bim. J Biol Chem,2006,281(14):9719-9727.
[32]He XW, Yu X, Liu T, et al. Vector-based RNA interference against vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of colorectal cancer in vivo in mice. Chin Med J.2008,121(5):439-444.
[33]Bo C, Xiaopeng D, Chuanliang P, et al. Expression of vascular endothelial growth factors C and D correlates with lymphangiogenesis and lymph node metastasis in lung adenocarcinoma. Thorac Cardiovasc Surg.2009,57(5):291-294.
[34]Liu Y, Ji R, Li J,et al. Correlation effect of EGFR and CXCR4 and CCR7 chemokine receptors in predicting breast cancer metastasis and prognosis. J Exp Clin Cancer Res.2010,29:16.
[35]Gerli R, Ibba L, Fruschelli C. Ultrastructural cytochemistry of anchoring filaments of human lymphatic capillaries and their relation to elastic fibers. Lymphology,1991,24(3):105-112.
[36]Sako A, Kitayama J, Ishikawa M, et al. Impact of immunohistochemically identified lymphatic invasion on nodal metastasis in early gastric cancer. Gastric Cancer,2006,9(4):295-302.
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