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

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.

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

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 HIF-1α was detected by immunohistochemical 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 immunohistochemical 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-1α in NSCLC