缺氧诱导因子1α、2α和血管内皮生长因子在食管鳞癌中的表达

Co-expression of Hypoxia-inducible Factors 1α, 2α and Vascular Endothelial Growth Factor in Esophageal Squamous Cell Carcinomas

背景:食管癌是一种常见的消化道恶性肿瘤,血管生成在食管鳞癌的发生、发展中具有重要作用。缺氧诱导因子(HIF)鄄1α、HIF鄄2α是机体对缺氧适应性调节中的重要调控蛋白,在大多数恶性肿瘤中有表达,可通过调节血管内皮生长因子(VEGF)的表达诱导肿瘤血管生成。目的:探讨食管鳞癌组织中HIF鄄1α、HIF鄄2α、VEGF的表达和微血管密度(MVD)之间的关系及其与肿瘤临床病理特征之间的关系。方法:应用免疫组化方法分别检测62例食管鳞癌、40例食管鳞状上皮异型增生和42例正常食管上皮组织中HIF鄄1α、HIF鄄2α、VEGF的表达和MVD值,分析其间的相关性及其与肿瘤临床病理特征之间的相关性。结果:食管鳞癌组织中HIF鄄1α、HIF鄄2α和VEGF的表达较异型增生和正常上皮组织显著增加(P<0.01),MVD值亦显著增高(P<0.01);且HIF鄄1α和VEGF的表达与肿瘤浸润深度、淋巴结转移和TNM分期呈正相关,HIF鄄1α和HIF鄄2α的表达与VEGF的表达和MVD值呈正相关。结论:HIF鄄1α、HIF鄄2α在食管鳞癌组织中存在一定程度的表达,其可能通过诱导VEGF的表达参与食管鳞癌的血管生成;HIF鄄1α、HIF鄄2α和VEGF的过度表达可能成为判断食管鳞癌生物学行为的重要指标。

Background: Esophageal carcinoma is a common gastrointestinal malignant tumors. The angiogenesis plays a vital role in the development and progression of esophageal squamous cell carcinomas (ESCC). Hypoxia-inducible factors (HIF)-1α and HIF-2α are important modulins involved in the regulation of the transcription of a variety of genes in response to hypoxia. They are expressed in most of the malignant tumors and can induce neo-angiogenesis by activation of vascular endothelial growth factor (VEGF). Aims: To investigate the correlations among the expression of HIF-1α, HIF-2α, VEGF and microvessel density (MVD) and their relationships to the clinicopathologic features of ESCC. Methods: Using immunohistochemical method, the expression of HIF-1α, HIF-2α, VEGF and MVD in 62 samples of ESCC, 40 dysplasia and 42 normal esophageal mucosal epithelia were assessed. The correlations between the expression of HIF-1α, HIF-2α, VEGF and MVD, and their relationships to the clinicopathologic characteristics of ESCC were analyzed. Results: The expression of HIF-1α , HIF-2α and VEGF in ESCC were significantly higher than those in atypical dysplasia and normal esophageal mucosal epithelium(P<0.01), and so did the MVD value(P<0.01). The expression of HIF-1α and VEGF were positively correlated with the depth of tumor invasion, lymph node metastasis and TNM classification of ESCC. The expressions of HIF-1α and HIF-2α were positively correlated with the expression of VEGF and the value of MVD. Conclusions: HIF-1α and HIF-2α are partly expressed in ESCC and their expressions may be involved in the angiogenesis of ESCC through VEGF activation pathway. The overexpression of HIF-1α , HIF-2α and VEGF can be used as important indices for evaluating the biological behaviors of ESCC.