食管鳞癌组织中HIF-1α与VEGF及MVD的表达及其意义

Expressions of HIF-1α and VEGF as well as their correlation with angiogenesis in esophageal squamous cell carcinomas

目的:探讨缺氧诱导因子(hypoxia-inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial cell growth fac-tor,VEGF)在食管鳞癌组织中的表达及其与肿瘤血管新生和临床病理特征之间的关系。方法:应用免疫组化分别检测50例食管鳞癌、30例食管上皮内瘤变和35例正常食管上皮组织标本中HIF-1α、VEGF的表达和微血管密度(microvessel density,MVD)值,分析其相关性及其与肿瘤血管生存和肿瘤临床病理特征之间的关系。结果:食管鳞癌组织中,HIF-1α和VEGF的阳性率及MVD值分别为80%(40/50)、84%(42/50)和71.10±15.02,较上皮内瘤变组[53.3%(16/30)、66.7%(20/30)和49.47±13.78]及正常上皮组[0(0/35)、25.7%(9/35)和24.46±7.50]显著增加,P<0.01。HIF-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,且HIF-1α的表达与VEGF的表达和MVD值呈正相关,P<0.05。结论:HIF-1α可通过上调VEGF的表达促进食管鳞癌的微血管形成,可能在食管鳞癌的发生和发展中起重要作用。HIF-1α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。

OBJECTIVE： To investigate the expressions of hypoxia-inducible factor-1α （HIF-1α） and vascu1αr endothelial cell growth factor （VEGF）, and their re1αtions with the angiogenesis and the clinicopathologic characteristics of esophageal squamous cell carcinomas （ESCC）. METHODS： The expressions of HIF-1α, VEGF and microvessel density （MVD） were detected by the immunohistochemical method in 45 cases of esophageal squamous cell carcinomas （ESCC）, 30 intraepithelial neop1αsia and 35 nomal esophageal mucosal epithelia. The corre1αtions among the expressions of HIF-1α, VEGF and MVD, and their re1αtions with the clinicopathologic features of ESCC were analyzed. RESULTS： The rates of positive expressions of HIF-1α and VEGF which were 80%（40/50） and 84%（42/50） in ESCC were significantly higher than those in intraepithelial neop1αsia [53.3% （16/30） ,66.7 （20/30）] and normal esophageal mucosal epithelium [0 （0/35） ,25.70%（9/35）] and so did the MVD value which was 71.10±15.02 in ESCC, 49.47±13.78 in intraepithelial neop1αsia and 24. 46±7.50 in normal esophaeal mucosal epithelium, P〈0.01. The expressions of HIF-1α and VEGF were positively corre1αted with the depth of tumor invasion, lymph node metastasis and TNM c1αssification of ESCC. The expressions of HIF-1α were positively corre1αted with the expressions of VEGF and the value of MVD, P〈0. 05. CONCLUSIONS： HIF-1α may induce the angiogenesis in ESCC by upregu1αting the transcription of VEGF gene. It may p1αy an important role in the carcinogenesis and aggression in ESCC. HIF-1α, VEGF and MVD may be useful markers for evaluating the biological behaviors of ESCC.