上皮性卵巢癌CDH1基因启动子甲基化和蛋白表达的关系及意义

Association between CDH1 promoter methylation and E-cadherin protein expression and its clinical significance in primary epithelial ovarian carcinomas

目的:检测上皮性卵巢癌组织中上皮型钙粘附素基因(CDH1基因)启动子区甲基化分布情况,分析其与上皮性钙粘附素蛋白表达的关系,探讨启动子甲基化对于蛋白表达的影响和意义。方法:应用甲基化特异的PCR(MSP)检测38例正常卵巢上皮和80例上皮性卵巢癌组织中CDH1基因启动子区甲基化,采用免疫组织化学方法检测上述标本中Ecadherin表达的情况,并结合肿瘤的生物学行为进行分析。结果:Ecadherin在上皮性卵巢恶性肿瘤中表达明显降低(P<0.05);34例CDH1基因启动子甲基化全部出现在卵巢癌组,有淋巴结转移组中甲基化频率明显高于无淋巴结转移组(26/35vs8/45,P<0.05);卵巢癌组织中有CDH1基因启动子甲基化者,Ecadherin表达明显低于无甲基化者(P<0.05)。结论:Ecadherin表达降低与上皮性卵巢癌转移关系密切,CDH1基因启动子区甲基化可能是导致Ecadherin表达蛋白表达减低的重要原因之一。

Objective:To detect the methylation pattern of the E-cadherin (CDH1) gene and its possible correlation with the expression of E-cadherin protein in the primary epithelial ovarian carcinomas and to evaluate the effect of CDH1 promoter methylation on E-cadherin protein expression. Methods:CDH1 promoter methylation was detected by Methylation-Specific Polymerase Chain Reaction (MSP) in 80 patients with primary epithelial ovarian carcinomas and 38 cases of normal ovarian epithelium. The expression of E-cadherin was examined by immunohistochemistry and analyzed by comparison with tumor biological behaviors. Results:Expression of E-cadherin was reduced significantly in the epithelial ovarian carcinoma tissues compared with the normal control (P<0.05). CDH1 promoter methylation was observed in 34 cases of epithelial ovarian carcinomas. The patients with lymph node metastases showed higher frequency of CDH1 promoter methylation than those without lymph node metastases. The patients with CDH1 promoter methylation showed lower expression of E-cadherin than those without CDH1 promoter methylation(P<0.05). Conclusions:Down-regulation of E-cadherin protein expression was closely associated with metastasis of primary epithelial ovarian carcinoma. Abnormal methylation of CDH1 promoter was one of the important reasons for the down-regulation of E-cadherin protein expression.