乳腺癌组织中缺氧诱导因子-1α和葡萄糖转运蛋白1表达及其意义

Expression of hypoxia-inducible factor 1 alpha and glucose transporter 1 and its significance in human breast carcinoma

目的探讨乳腺癌组织中缺氧诱导因子-1α（HIF-1α）和葡萄糖转运蛋白1（Glut1）表达的关联性及其与细胞增生活性和临床病理因素的关系。方法采用免疫组织化学方法检测HIF-1α、Glut1、增生细胞核抗原（PCNA）在80例乳腺癌组织、20例乳腺纤维腺瘤及20例乳腺增生组织中的表达水平并比较它们之间的相关性。结果HIF-1α和Glut1在乳腺纤维腺瘤、乳腺增生组织中不表达；HIF-1α在乳腺导管内原位癌中阳性率55．0％（11／20），浸润性乳腺癌中85．0％（51／60）；乳腺癌中Glut1阳性率58．8％（47／80）；乳腺癌中PCNA阳性率75％（60／80），其中原位癌65％（13／20），浸润癌78．3％（47／60）。乳腺癌中HIF-1α表达与Glut1呈显著正相关（r=0．653，P〈0．01）；HIF-1α表达与PCNA呈显著正相关（r=0．693，P〈0．01）；Glut1与PCNA呈显著正性相关（r=0．742，P〈0．01）。HIF-1α和Glut1在淋巴结、雌激素受体状态及组织学分级中表达差异有统计学意义；Glut1在肿瘤大小及孕激素受体状态表达差异也有统计学意义。结论HIF-1α和Glut1蛋白的过表达共同参与了乳腺癌的发生、发展，与乳腺癌细胞增生活性密切相关，有望成为乳腺癌治疗的新靶点。

Objective To investigate the expression of hypoxia- inducible 1 alpha （HIF-1α） and glucose transporter 1 （Glut1） in human breast cancer and its relationship to proliferating cell nuclear antigen （PCNA） protein and clinical pathologic factors. Methods Immunohistochemical staining was used to measure the expression of HIF-1α, Glut1 and PCNA in human breast fibroadenoma, usual hyperplasia and breast carcinoma. Results HIF-1α expression was not found in breast fibroadenoma and hyperplastie lesions. In contrast, the positive rate of HIF-1α was found in the duetal carcinoma in situ 55 %（DCIS, 11/20） and the invasive breast carcinoma 85 %（51/60）. Glut1 positivity in breast carcinoma was 58.8 %（47/80）. The total positive rate of PCNA in breast carcinoma was 75 %（60/80）, that in DCIS was 65 %（13/20） and that in invasive carcinoma was 78.3 %（47/60）. There was a positive correlation between HIF-1α and Glut1 level （r = 0.653, P 〈0.01）, a positive correlation between HIF-1α and PCNA level （r = 0.693, P 〈0.01）; and also a positive correlation between Glut1 and PCNA level （r = 0.742, P 〈0.01）. Conclusion The overexpression of HIF-1α and its target gene Glut1 played important roles in carcinogenesis and progression of breast carcinoma and closely correlated with cell proliferation of breast carcinoma and may become a new target for treatment of breast carcinoma.