上皮钙黏素1基因启动子甲基化对结肠癌上皮钙黏素和β-连接素表达的影响

Effects of CDH1 gene promoter methylation on expression of E-cadherin and beta-catenin and its clinicopathological significance in colon carcinoma

目的探讨上皮钙黏素基因（CDH1）启动子甲基化与结肠癌上皮钙黏素（E—cadherin）及β-连接素（β-catenin）的表达及临床病理特征的关系。方法采用甲基化特异性PCR技术检测68例结肠腺癌组织、癌旁组织及正常黏膜组织中CDH1基因启动子甲基化的状况。采用免疫组织化学法检测E-cadherin及β—catenin蛋白的表达．结果癌旁组织及癌组织中CDH1启动子甲基化的阳性表达分别为32．4％（22／68）、57．4％（39／68），正常组织均为阴性表达（P〈0．05）。E—cadherin在正常组织、癌旁组织及腺癌组织中阳性表达率分别为92．6％、66．2％和44．1％。正常组织中β—catenin均表达于细胞膜上，无胞质和（或）胞核表达。而β—catenin在癌旁组织及癌组织中胞质和（或）胞核表达分别为29．4％和50．0％。CDH1基因启动子甲基化阳性率与E-cadheftn表达则呈负相关（r=-0．312，P=0．01），与β-catenin胞质和（或）胞核表达呈正相关（r=0．309，P=0．018）。CDH1基因启动子甲基化及E-cadherin、β-catenin的异常表达均与结肠癌分化程度及转移密切相关（P〈0．05）。结论CDH1基因启动子甲基化可能是导致结肠癌E-cadheftn与β-catenin异常表达及肿瘤侵袭性增强的重要原因。

Objective To investigate the relationship between methylation of the CDH1 gene promoter on the expression of E-cadherin and β-catenin, and to evaluate the correlation with clinicopathological characteristics of the colonic carcinoma. Methods Methylation specific PCR （MSP） was used to detect CDH1 gene promoter methylation in the cancer tissue, adjacent tissues and normal tissues in 68 patients. The expression of E-cadherin and β-catenin was determined by immunohistochemistry staining. Results The positive rate of CDH1 gene promoter methylation was 32.4% in adjacent tissues and 57.4% in cancer tissue, while no detectable methylation was found in all the normal tissues. The difference was statistically significant. The positive rate of E-cadherin was 92.6% in the normal tissues, 66.2% in the adjacent tissues and 44.1% in the cancer tissues. In all normal tissues, β-catenin was expressed only at the cellular membrane but not in the cytosol or nucleus, while the expression of β-catenin was present in the cytosol or nucleus in 29.4% of the adjacent tissues and 50.0% of the cancer tissues. The positive rate of CDHI gene promoter methylation was negatively correlated with E-cadherin expression （r=-0.312,P=0.01） and positively correlated with β-catenin cytosolic/nueleus expression（r=0.309,P=0.018）. The differentiation and metastasis of colonic carcinoma were associated with the aberrant expression of E-eadherin, β-catenin, and methylation of CDH1 promoter （P〈0.05）. Conclusion CDH1 gene promoter methylation may lead to aberrant expression of E-cadherin and β-catenin in colonic carcinoma, and may play an important role in promoting the invasion of tumor.