脑胶质瘤中hMLH1基因表达及启动子区的甲基化状态研究

目的检测脑胶质瘤中hMLH1基因表达及其启动子区的甲基化状态,探讨其在肿瘤发生中的作用。方法采用免疫组化及甲基化特异性聚合酶链反应方法,检测51例脑胶质瘤hMLH1基因表达和启动子区甲基化状态。结果 hMLH1阳性表达率为78.4%(40/51),甲基化率为13.7%(7/51),均与性别、年龄、病理类型无相关性。hMLH1在低级别(Ⅰ~Ⅱ级)胶质瘤和高级别(Ⅲ~Ⅳ级)胶质瘤中的阳性表达率分别为92.0%(23/25)和65.4%(17/26),两者差异显著(P0.05)。hMLH1在低级别(Ⅰ~Ⅱ级)和高级别胶质瘤中hMLH1启动子区甲基化率分别为0.0%(0/25)和26.9%(7/26),两者差异显著(P0.05)。hMLH1表达阳性的胶质瘤和表达阴性的胶质瘤中启动子区甲基化率分别为7.5%(3/40)和36.4%(4/11),两者差异显著(P0.05)。结论 hMLH1基因在胶质瘤中表达及启动子区甲基化状态与胶质瘤病理分级有关,hMLH1可能在胶质瘤的发展中起作用,其启动子区甲基化可能负调控hMLH1基因表达。

Expression of mismatch repair gene hMLHl and methylation status of its promoter region in gliomas

Objective To investigate the roles of the expression of hMLH1 gene and methylation status of its promoter region in the glioma pathogenesis.Methods The expressions of hMLH1 gene and the methylation status of its promoter region were determined by immunohistochemical technique and methylation-specific PCR in 51 specimens of gliomas.Results The rates of positive expression of hMLH1 gene and methylation of its promoter region in the gliomas,which were 78.4%（40/51）and 13.7%（7/51）respectively,were not related to pathological type of gliomas,and sex and age of the patients with gliomas.The rate92.0%（23/25）]of positive expression of hMLH1 gene in gradesⅠ-Ⅱgliomas was significantly higher than that65.4%（1 7/26）]in gradesⅢ-Ⅳgliomas（P0.05）.The rate（0.0%）of hMLH1 promoter methylation in gradesⅠ-Ⅱgliomas was significantly lower than that（26.9%）in gradesⅢ-Ⅳgliomas（P0.05）.The rate7.5%（3/40）]of hMLH1 promoter region methylation was in 40 gliomas with positive expression hMLH1 gene was significantly lower than that36.4%（4/1 1）]in 1 1 gliomas with negative expression of hMLH1 gene（P0.05）.Conclusions Thee xpression and promoter region methylation of hMLH1 gene in the gliomas are related to pathological grades.Maybe the expression of hMLH1 gene is related to the pathological development of glioma,and are down regulates by the promoter region methylation.