VEGF-C介导的乳腺癌肿瘤淋巴管生成及定位

目的：探讨血管内皮生长因子C（vascular endothelial growth factor C，VEGF-C）介导的乳腺癌肿瘤淋巴管生成及定位。方法：分子生物学原位杂交方法检测VEGF-C mRNA基因在89例原发性乳腺癌组织中的表达；免疫组化SP法对乳腺癌肿瘤淋巴管进行血管内皮生长因子受体3（vascular endothelial growth factor receptor-3，VEG-FR-3）标记。结果：在89例原发性乳腺癌组织中，49例表达VEGF-C mRNA，表达率为55．06％。VEGF-C mRNA的表达与乳腺癌淋巴管密度（lymphatic vessel density，LVD）和腋淋巴结转移呈正相关；与VEGF-CmRNA阴性组相比，VEGF-C mRNA阳性组的肿瘤淋巴管密度大、腋淋巴结转移率高（均P〈0．05）；所有病例都有不同程度的淋巴管生成，但以肿瘤间质组织中淋巴管生成为主，癌巢中未见到明显的成形淋巴管。肿瘤淋巴管密度与乳腺癌临床分期和腋淋巴结转移呈正相关，临床分期越晚，肿瘤淋巴管密度越高（P〈0．05）；腋淋巴结转移组的肿瘤淋巴管密度比无淋巴结转移组高（P〈0．05）。结论：原发性乳腺癌组织VEGF-C mRNA的表达与乳腺癌肿瘤淋巴管生成、腋淋巴结转移呈正相关；VEGF-C介导的乳腺癌肿瘤淋巴管生成主要发生在肿瘤间质组织中。

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Objective To investigate the lymphangiogenesis and location of tumor lymphatic vessels induced by vascular endothelial growth factor C(VEGF-C) in primary breast cancer.Methods The expression of VEGF-C mRNA in 89 cases of primary breast cancer was detected by in situ hybridization,and lymphatic vessels with vascular endothelial growth factor receptor-3(VEGFR-3) were labeled by immunohistochemistry SP method.Results VEGF-C mRNA expressed in 49 of all 89 cases of primary breast cancer,and the expression rate was 55.06%.The expression of VEGF-C mRNA was positively correlated with lymphatic vessel density(LVD) and axillary lymph node metastasis,LVD and the rate of axillary lymph node metastasis were significantly higher in VEGF-C mRNA positive group than those in the negative group(both P<0.05).Different levels of lymphangiogenesis took place in all cases of breast cancer,but it was mainly located in tumor stroma,and apparently mature lymphatic vessels were not found in cancer nests.LVD was positive related with the clinical stage and axillary lymph node metastasis in breast cancer;the clinical stage,the LVD,the axillary lymph node metastasis in positive group were higher than those in the negative group(P<0.05).Conclusion The expression of VEGF-C mRNA is positively correlated with lymphangiogenesis and axillary lymph node metastasis in primary breast cancer.Lymphangiogenesis induced by VEGF-C predominantly takes place in the tumor stroma tissue,and mature lymphatic vessels are not found in cancer nests.