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

Relation of lymphatic microvessel density detected by monoclonal antibody D2-40 with VEGF-C expression in breast cancer

目的探讨人乳腺癌组织中D2-40标记的微淋巴管密度（LMVD）与血管内皮生长因子C（VEGF-C）表达的关系。方法收集102例乳腺癌、25例乳腺纤维腺瘤和10例正常乳腺组织标本，采用免疫组化SP法检测D2-40单抗标记的LMVD和VEGF-C蛋白的表达水平，采用原位杂交法检测VEGF-CmRNA的转录水平。结果102例人乳腺癌组织中，D2-40标记微淋巴管的阳性率为76．5％，高于乳腺纤维腺瘤组织。癌周组织的LMVD为30．1个微淋巴管／100倍视野，显著高于癌中心区、正常乳腺组织和乳腺纤维腺瘤组织的LMVD（均P〈0．01），且与乳腺癌腋窝淋巴结转移数目明显相关（r=0．964，P〈0．01）。102例乳腺癌组织中，VEGF-C蛋白和mRNA的阳性表达率分别为55．9％和59．8％，均高于乳腺纤维腺瘤组织（X^2=11．653，P=0．003；X^2=10．345，P=0．006），且与淋巴结转移数目、临床分期、c-erbB-2和p53基因的表达相关（均P〈0．05）。VEGF-C蛋白和mRNA的表达水平均与D2-40标记的LMVD相关（P〈0．05），尤其见于癌周组织中（P〈0．01）。结论D2-40单抗标记的LMVD与VEGF-C的表达有密切关系，VEGF-C参与的乳腺癌微淋巴管的生成在乳腺癌淋巴转移中有重要意义。

Objective To investigate the relationship of lymphatic micovessel density （I2dVD） detected by monoclonal antibody D2-40 with the VEGF-C expression in human breast cancer. Methods Tissue samples of 102 breast cancers, 25 breast fibroadenomas and 10 normal breasts were collected. Immunohistochemical staining was used to detected the lymphatic micovessels with monoclonal antibody D2- 40. The expression of VEGF-C was detect by SP immunohistochemistry, and VEGF-C mRNA by hybridization in situ. Results In 102 breast cancers, the positive rate of D2-40 was 76.5% （78/102） , higher than that in the breast fibroadenomas. LMVD in the periphery of breast cancer was 30. 1 lymphatic microvessels per x 100 field of vision, which was significantly higher than that in the central area of the tumors （P =0.000）. The LMVD in the periphery of the breast cancers was correlated with the number of metastatic lymph nodes （r = 0.964,P 〈 0.01 ）. The positive rates of VEGF-C protein and mRNA were 55.9% （57/102） and 59.8% （61/102）, respectively, significantly higher than that in the breast fiberoadenomas and normal breast tissues （X^2 = 11. 653, P = 0. 003; X^2 = 10. 345, P = 0. 006） , and were significantly correlated with the status of lymph node metastasis, clinical stage and the expressions of c-erbB-2 and p53 protein （P 〈 0.05）. Both of VEGF-C protein and mRNA were significantly correlated with LMVD detected by D2-40 （ P 〈 0. 05 ）, especially with the LMVD in the periphery of breast cancers （ P 〈 0. 05 ）. Conclusion The monoclonal antibody D2-40 can be used to detect the lymphatic endothelium in human breast cancer. The lymphatic microvessel density in the periphery of breast cancer is correlated with the lymph node metastasis and expression of VEGF-C. Therefore, VEGF-C may play a significant role in the lymphangiogenesis leading to metastasis of breast cancer.