肝内胆管癌中上皮-钙黏附素基因CDH1的甲基化研究

目的:探讨肝内胆管癌组织中上皮-钙黏附素(epithelial-cadherin,E-cadherin基因CDH1的甲基化状况.方法:42例肝内胆管癌标本系东方肝胆外科医院术后肿瘤组织和癌旁组织的石蜡包埋及新鲜冰冻标本.男性32例,女性10例.分别采用MSP、RT-PCR以及EnVision方法检测42例肝内胆管癌患者术后标本中CDH1基因甲基化以及E-cadherin的mRNA及蛋白表达变化.结果:肝内胆管癌中CDH1甲基化发生率为28.6%.E-cadherin的mRNA及蛋白表达减低率分别为64.3%和69.1%.CDH1基因甲基化与E-cadherin蛋白表达、mRNA表达以及胆管癌肝内转移之间存在显著相关(分别P=0.008,P=0.031和P=0.020).CDH1甲基化与生存预后之间无相关性,E-cadherin表达异常与患者不良生存则显著相关(P=0.002).结论:肝内胆管癌中常发生CDH1高甲基化及E-cadherin表达异常,表明CDH1甲基化及E-cadherin的表达异常与肝内胆管癌的发生发展密切相关.

CDH1 methylation of E-cadherin gene in human intrahepatic cholangiocarcinomas: correlation between clinicopathologic parameters and patients' survival

Objective:To investigate CDH1 methylation of epithelial-cadherin(E-cadherin) gene in intrahepatic cholangiocarcinomas (ICCs). Methods: Forty-two liver samples were obtained from ICC patients (32 males and 10 females) during surgical resection in Eastern Hepatobiliary Surgery Hospital. The ICC tissue samples and the adjacent tissue samples were paraffin-embedded and fresh ice-frozen. A methylation-specific polymerase chain reaction (MSP) was used for analyzing the methylation of CDH1 gene; E-cadherin protein and mRNA expression was detected by immunohistochemical method and RT-PCR analysis, respectively. Results: The methylation rate of CDH1 was 28.6% in ICC patients. The expression of E-cadherin mRNA and protein was decreased in 64.3% and 69.1% of the samples, respectively. The methylation of CDH1 gene was correlated with the expression of E-cadherin protein and mRNA and metastasis of ICCs (P=0.008, P=0.031, and P=0.020, respectively),but not with the prognosis of ICC. The abnormal expression of E-cadherin was significantly correlated with the survival of patients(P=0.002). Conclusion: The methylation of CDH1 gene and down-regulation of E-cadherin are frequently seen in ICC patients, indicating that they may be closely related to the development and progression of ICCs.