HIF-1α,VEGF的表达及与乳腺癌生物学行为的关系

The Relationship Between the Expression of HIF- 1α,VEGF and the Biological behavior of Breast Cancer

目的探讨乳腺癌组织中缺氧诱导因子-1α(hypoxia-inducible factor-1 alpha,HIF-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达及其与乳腺癌生物学行为之间的关系。方法采用免疫组化SP法检测乳腺纤维腺瘤、癌旁正常乳腺组织和乳腺癌中HIF-1α,VEGF蛋白的表达。结果HIF-1 α蛋白在乳腺纤维腺瘤、癌旁正常乳腺组织中几乎无表达,乳腺导管原位癌中阳性率46.67%(14/30),导管癌早期浸润中63.33%(19/30),浸润性乳腺癌中76.67%(23/30);乳腺癌中VEGF阳性率67.78%(61/90);乳腺癌中HIF-1α表达与VEGF(r=0.64,P<0.01)呈正相关,与c-erbB-2正相关(r=0.276,P<0.01);HIF-1α及其靶基因VEGF在乳腺癌组织中明显上调,HIF-1α表达与淋巴结转移、雌激素受体状态、组织学分级及临床分期相关。结论HIF-1 α和VEGF的表达与乳腺癌的生物学行为有关,HIF-1α可能成为早期诊断乳腺癌、预测其转移的重要指标。

Objective To investigate the expression of hypoxia-inducible factor-1 alpha（HIF-1α） and vascular endothelial growth factor（VEGF） protein in human breast cancer,to find out whether there is significant correlation between HIF -1α and VEGF and to reveal the relationship between the two factors and the biological behavior of breast cancer. Methods Immunohistochemical streptavidin-peroxidase（SP） was used to detect the expression of HIF-1 α, VEGF in human breast fibroadenoma,adjacent normal breast tissue and breast carcinoma. Results Little expression of HIF-1α was observed in breast fibroadenoma and the adjacent normal breast tissue ; In contrast, the positive rate of HIF-1α found in the ductal carcinoma in situ was 46.67% （14/30） ,in early invasive carcinoma was 63.33% （ 19/30） and in the invasive breast carcinoma was 76.67% （ 23/30 ）. The positive expression rate of VEGF in breast carcinoma was 67.78% （ 61/90 ）. The increased level of HIF-1α was significantly associated with the increased expression of VEGF and c-erbB-2（ r = 0.64 ,P 〈 0.01 ;r=0. 276 ,P 〈 0.01 ）. The up-regulation of the expression of HIF-1α and its target gene（VEGF） in breast carcinoma has a close relationship with tumor angiogenesis. HIF-1α is associated with lymph node metastasis, ER status and stages of histology. Conclusion The level of HIF - 1α and VEGF relates with the biological behavior of breast cancer. They could be taken as useful marker for predicting the invasion, metastasis and prognosis of breast cancer.