缺氧诱导因子-1α在肺癌组织中的表达及其与肺癌淋巴道转移关系的研究

Expression of Hypoxia Inducible Factor-1 alpha and Its Correlation with Lymphangiogenesis in Lung Cancer

目的研究缺氧诱导因子-1α(HIF-1α)与肺癌淋巴道转移的关系及其可能的作用机制。方法采用免疫组织化学方法检测72例肺癌组织、癌周组织和20例正常肺组织中HIF-1α、血管内皮生长因子-C(VEGF-C)及转化生长因子-α(TGF-α)的表达,采用D2-40免疫组织化学法标记组织标本中的淋巴管并测定微淋巴管密度(LMVD),对各因子表达水平的相关性及癌周组织中LMVD与临床病理特征的关系进行统计学分析。结果 D2-40免疫组化染色显示,微淋巴管主要集中在癌周组织,癌周组织LMVD的高低与肺癌淋巴结转移具有正相关性。HIF-1α、VEGF-C和TGF-α在肺癌组织中的表达水平明显高于正常肺组织(均P<0.05);HIF-1α的表达水平与VEGF-C、TGF-α表达水平及癌周组织LMVD呈正相关(r值分别为0.452、0.396及0.444,均P<0.05),VEGF-C的表达与TGF-α表达水平及癌周组织LM-VD呈正相关(r值分别为0.357及0.523,均P<0.05)。结论 HIF-1α在肺癌组织中的表达与肺癌淋巴结转移显著相关。HIF-1α可能通过上调肺癌组织中TGF-α和VEGF-C的表达,从而参与肺癌的淋巴道转移过程。

Objective To investigate the relationship between hypoxia inducible factor-1α（HIF-1α）and lymphangiogenesis and discuss the potential mechanism in lung cancer.Methods The expression levels of HIF-1α,transforming growth factor-α（TGF-α）and vascular endothelial growth factor-C（VEGF-C）proteins were detected by immunohistochemical SABC method in 72 cases of lung cancer tissues,72 cases of peritumoral tissues and 20 cases of normal lung tissues.The lymphatic vessel was assessed by immunohistochemical staining with an antibody against D2-40,and then lymphatic microvessel density（LMVD）was measured.Results The level of LMVD was positively correlated with lymph node metastasis.The expression levels of HIF-1α,TGF-α and VEGF-C in tumor specimens were significantly higher than in normal lung tissues（P〈0.05）.The HIF-1α expression was correlated with VEGF-C expression,TGF-α expression and LMVD（r=0.452,0.396 and 0.444,respectively,P〈0.05）.Furthermore,the VEGF-C expression was correlated with TGF-α expression and LMVD（r=0.357 and 0.523,P〈0.05）.Conclusion HIF-1α maybe play a role in lymphatic invasion and lymph node metastasis through the induction of VEGF-C and TGF-α in lung cancer.