原发性结肠腺癌中E—cadherin基因异常甲基化及蛋白表达的研究

目的探讨原发性结肠腺癌组织与相应癌旁组织中E-cadherin（E-cad）基因异常甲基化改变及其蛋白表达的特点。以及其与结肠腺癌发生发展的关系。方法分别采用甲基化特异PCR（MSP）和免疫组化SP法检测40例原发性结肠腺癌和相应癌旁组织中E—cad基因甲基化状态及蛋白表达水平，并结合临床资料进行分析。结果结肠腺癌中E-cad甲基化率为70．0％，癌旁组织中为10．0％，两者有显著差异性（P〈0．01）；结肠腺癌中E—cad蛋白的表达率为32．5％，癌旁组织中为80．0％；两者有显著差异性（P〈0．01）。E—cad蛋白缺失的27例标本中有24例甲基化阳性。甲基化与蛋白缺失有明显关系（P〈0．01）。E-cad甲基化程度与患者的性别、年龄、肿瘤的大小之间差异无显著意义（P〉0．05），但与肿瘤浸润深度、分化程度、淋巴结转移之间差异有显著意义（P〈0．05）。结论E—cad基因的异常甲基化可影响蛋白的表达，它们与结肠腺癌的发生发展有关，E—cad甲基化和蛋白表达可能作为结肠腺癌预后的候选标志物之一。

E-Cadherin gene hypermethylation and its protein expressiom in primary colon adenocarcinoma

Objective To investigate the methylation of the E-cadherin（E-cad） gene and E-cad protein expression in human colon adenearcinoma and the corresponding tumor-adjacent tissues,and evaluate their role in tumor carcinogenesis, and progression and its clinical significance.Methods Methylation-specific PCR （MSP） was used to detect E-cad methylation of 40 parafin-embedded primary colon carcinoma specimens,immunohistochemistry was used to detect the expression of E-cad protein of the correspond- ing tumor-adjacent tissues,and analyze their relations with clinicopathological characteristics.Results The methylation rate was70.0% （28/40）in colon carcinoma and 10.0%（4/40） in corresponding tumor-adjacent tissues.Expression rate of E-cad protein was 32.5% （13/ 40）in colon carcinoma,80.0%（32/40） in corresponding tumor-adjacent tissues.The E-cad gene methylation was closely related to E- cad protein expression in colon carcinoma（P〈0.01 ）.The aberrant methylation in the promoter of E-cad gene and the expression of E- cad protein were no relationship with those clinicopathological characteristics： patient＇s sex,age,the tumor size（P〉0.05） ;but were significantly related to the infiltrating depth, the histological differentiation and lymph node metastasis （P〈0.05）. Conclusion Methylation in E-cad gene and E-cad protein expression were associated with the development of colon adenocareinoma and could be used as a putative prognostic indicator for malignancy.