人非小细胞肺癌中HIF-1α的表达与血管生成和细胞凋亡的关系及意义  

THE EXPRESSION OF HYPOXIA-INDUCIBLE FACTOR 1α AND ITS RELATIONSHIP WITH ANGIOGENESIS AND APOPTOSIS IN NON-SMALL CELL LUNG CANCER IN HUMEN

作　　者：姜颖[1] 张海青[1] 常秀军[1] 陈学静[1] 王重利 马燕杰[1] 

机构地区：[1]北京市结核病胸部肿瘤研究所病理科,北京101149

出　　处：《解剖学报》2007年第4期461-465,共5页Acta Anatomica Sinica

摘　　要：目的探讨缺氧诱导因子1α(HIF-1α)在非小细胞肺癌(NSCLC)中的表达及其与血管生成和细胞凋亡的关系,评估它在NSCLC发生发展过程中的作用。方法采用免疫组织化学的方法检测HIF-1α在正常肺组织、良性病变、癌前病变、原位癌、非小细胞肺癌及肺癌转移淋巴结中的表达,及血管内皮生长因子(VEGF)在NSCLC中的表达;采用TUNEL法检测部分NSCLC中细胞凋亡指数AI。结果HIF-1α在支气管黏膜非典型增生、原位癌、NSCLC及肺癌转移淋巴结中的阳性表达率相似,总阳性表达率为40.0%(68/170),其在正常及良性病变中的总阳性表达率为6.0%(4/67),两组间有显著差异(P<0.01)。HIF-1α在NSCLC中的表达与各项临床病理特征均无明显相关性,仅与患者术后生存时间明显正相关(P<0.01)。VEGF在NSCLC中的表达与HIF-1α的表达呈正相关(P<0.01),与患者预后呈负相关(P=0.027)。凋亡指数(AI)在各组织类型和各分化程度的Ⅰ期肺癌中无明显差异,但生存期≥5年的肺癌患者AI明显高于生存期<5年的患者(P=0.004)。AI与HIF-1α的表达明显正相关(P=0.004)。结论HIF-1α在非小细胞肺癌组织中的表达较正常及良性病变肺组织明显上调,其与肿瘤血管生成及细胞凋亡均密切相关,在NSCLC生长中的作用具有多向性。HIF-1α可以作为评估患者预后的重要指标。Objective The aim of the study is to investigate the expression of HIF-1α and its relationgship to angiogenesis and apoptosis in non-small cell lung cancer（NSCLC）, and evaluate its roles in the transformation of NSCLC. Methods The expression of HIFo I a was detected by staining in the normal lung tissues, the benign lesion, the precancerous lesion, the carcinoma in situ, NSCLC and lymph nodes with metastatic lung cancer. The expression of VEGF was detected by staining in lung cancer. Apoptotic cells were detected with a nonradioactive 3＇-end DNA labeling technique （TUNEL reaction） in part of NSCLC. Results The positive rates of HIF-1α found in the precancerous lesion, the carcinoma in situ, lung cancer and the lymph nodes with metastatic lung cancer, were remarkably higher than those in the normal lung tissues and the benign lung lesion. The expression of HIF-1α was only correlated positively with survival time of patients. The expression of VEGF was correlated positively with that of HIF-1α, and negatively to the prognosis of patients. Apoptotic index（AI） was not related to the histological classification and differentiation in stage Ⅰ lung cancer, but AI in the patients whose survival time was above 5 years was remarkably higher than that in the patients whose survival time was below 5 years. AI was correlated positively with the expression of HIF-1α. Conclusion The positive rate of HIF-la in NSCLC is much higher than those in the normal tissues and the benign lesion. HIF-1α is closely correlated with angiogenesis and apoptosis, and it plays several roles in carcinogenesis and the development of NSCLC. It is an important prognostic parameter in NSCLC.

关 键 词：肺肿瘤 缺氧诱导因子-1Α 血管内皮生长因子 凋亡 免疫组织化学 人 

分 类 号：R734.2[医药卫生—肿瘤]