血管内皮生长因子及其受体Flt-1在乳腺癌中的表达及意义

目的　试图揭示血管内皮生长因子 (VEGF)及其受体 (Flt 1)在乳腺癌组织中的表达规律 ,探讨其与血管生成和肿瘤浸润、转移等生物学行为的关系。方法　应用原位杂交和免疫组织化学技术 ,检测 4 8例乳腺癌组织中VEGF和Flt 1的mRNA和蛋白表达特性。结果　乳腺癌细胞高表达VEGFmRNA和蛋白 ,阳性率分别为 75 %、70 8% ,而血管内皮细胞几乎不表达 ;血管内皮细胞主要表达受体Flt 1mRNA和蛋白 ,阳性血管数分别为 2 6个 / 0 72mm2 ± 12个 / 0 72mm2 、2 4个 / 0 72mm2 ± 12个 / 0 72mm2 ,而少数癌细胞有少量表达 ;VEGF和Flt 1高表达组血管密度明显高于低表达组 ;VEGF和Flt 1表达与组织学分级和淋巴结转移密切相关。结论　VEGF以旁分泌途径促进乳腺癌血管形成 ,并参与肿瘤浸润和淋巴道转移过程 ,检测VEGF和Flt 1表达可做为判定乳腺癌血管生成、恶性度以及浸润转移等生物学行为的可靠指标。

Expression of vascular endothelial growth factor and its receptor (Flt-1) in breast carcinoma

OBJECTIVE: To investigate the expression of vascular endothelial cell growth factor (VEGF) and its receptor (Flt-1) in breast carcinoma and the relationship of such expression with angiogenesis, tumor invasion and metastasis. METHODS: In situ hybridization and immunohistochemistry technique were used to test the expression of mRNA and protein expression of VEGF and flt-1 in 48 specimens of breast carcinoma. 48 specimens of tissues near cancer, 3 specimens of fibroadenoma of breast, and 3 specimens of normal breast were used as controls. RESULTS: VEGF mRNA and its protein were expressed highly in breast carcinoma cells with the positive rate of 75% and 70.8% respectively. There was almost no expression of VEGF in vascular endothelial cells. Flt-1 mRNA and its protein were expressed only in a small quantity in a few tumor cells. The amount of blood vessel positive in Fit-1 mRNA and its protein was (26 +/- 12) piece/0.72 mm(2) and (24 +/- 12) piece/0.72 mm(2) respectively. The microvascular density (MVD) was significantly greater in VEGF and Flt-1 higher expression groups than in lower groups (P < 0.01). Both VEGF expression and Flt-1 expression were well correlated with the histological grade and lymph node metastasis. CONCLUSION: VEGF promotes angiogenesis by paracrining in breast carcinoma, and takes part in tumor invasion and lymph node metastasis. Test of the expression of VEGF and Flt-1 may act as a reliable index to determine angiogenesis, malignancy, invasion and metastasis. Blocking their secretion and effect may act as a new treatment for breast carcinoma.