脑肿瘤微卫星不稳定性和错配修复基因hMLH1、hMSH2蛋白表达的改变

Analyses of microsatellite instability and altered expression of hMLH1, hMSH2 in human brain tumors

目的 检测脑肿瘤微卫星不稳定性 (MIN)和错配修复 (MMR)基因蛋白表达的情况。方法 选取 12个微卫星多态性位点 ,以微卫星序列 PCR法和免疫组化技术检测 37例胶质瘤、 2 4例脑膜瘤及 6例神经鞘瘤中MIN和MMR基因hMLH1、hMSH2蛋白表达。结果 胶质瘤MIN发生率为 2 7%(10 / 37) ,脑膜瘤MIN阳性率仅为 4% (1/ 2 4) ,神经鞘瘤未见微卫星DNA异常。ABC免疫组化染色发现 10例hMLH1/hMSH2蛋白表达异常 (阴性 ) ,异常者均为MIN阳性病例。结论 不同恶性程度的胶质瘤均呈现基因组不稳定性 ,胶质瘤病理机制中包含MMR基因缺陷的参与。未发现MIN、MMR缺陷与脑膜瘤。

Objective To investigate the microsatellite instability and altered expression of mismatch repair genes in human brain tumors.Methods Using PCR denatruing PAGE with 12 polymorphic DNA markers to examine MIN, and immunohistochemical analysis to detect the expression of hMLH1, hMSH2 in 67 brain tumor tissues. Results MIN was observed in 10 of 37 gliomas (27%), 1 of 24 meningiomas (4%), but none in schwannomas. Ten of the 67 tumors showed aberrant expression pattern were MIN(+) gliomas.Conclusions Genomic instability should be regarded as a pathogenetic mechanism in human gliomas, and aberrant expression of MMR genes may be associated with human gliomas. Microsatellite instability and alteration of MMR genes was rare in meningiomas and schwannomas.