错配修复基因（MMR）蛋白在子宫内膜非典型增生中的表达及其意义

摘要

Objective To explore the expressions of mismatch repair gene proteins (MLH1,MSH2,PMS2 and MSH6),microsatellite instability (MSI)and its significance in atypical endometrial hyperplasia.Meth-ods Immunohistochemical method was adopted to detect the expressions of DNA mismatch repair proteins (MLH1,MSH2,PMS2 and MSH6)in atypical endometrial hyperplasia and in normal prolifera-tive endometrial tissues,and to analyze the relationship between MSI and clinical features of atypical endo-metrial hyperplasia.Results The rates of negative expression of MMR in endometrial atypical hyperplasia were as follows:MLH1 12%(6/50),MSH2 14%(7/50),PMS2 12%(6/50),MSH6 8%(4/50). Compared with the controls respectively,the differences among MLH1,PMS2 and MSH6 were statistically significant (P <0.05);while there was no significant difference between MSH2 group and others (P =0.338).Grouped by negative expression, the differences were statistically significant compared with normal proliferative endometrium group (P =0.005 ).Among them,there were 7 cases of MSI-H (14%),9 cases of MSI-L(18%),34 cases of MSS(68%).MSI-H of cases (≤50 years old)were signif-icantly higher than the others (P=0.001).Conclusion MSI and the negative expression of MMR proteins may be one of the important molecular events of atypical endometrial hyperplasia.%目的：探讨子宫内膜非典型增生中错配修复基因（mismatch repair gene，MMR）蛋白 MLH1、MSH2、PMS2和 MSH6的表达，微卫星不稳定性及意义。方法应用免疫组织化学法检测 DNA错配修复蛋白 MLH1、PMS2、MSH2和 MSH6在子宫内膜非典型增生（50例）及正常增生期宫内膜组织（50例）中的表达，分析微卫星不稳定性与子宫内膜非典型增生临床特征的关系。结果50例子宫内膜非典型增生组织中 MLH1、MSH2、PMS2、MSH6失表达率分别为12％（6/50）、14％（7/50）、12％（6/50）和8％（4/50）；MLH1、PMS2、MSH6的表达率高于正常增生期子宫内膜，差异具有统计学意义（P ＜0．05），两组MSH2的表达差异无统计学意义（P ＝0．338）。以蛋白失表达情况分组，子宫内膜非典型增生组 MSI-H 表型7例（14％），MSI-L 表型9例（18％），MSS 表型34例（68％），与正常增生期宫内膜组比较，差异具有统计学意义（P ＝0．005）。在子宫内膜非典型增生中，年龄≤50岁者 MSI-H明显高于＞50岁者（P ＝0．001）。结论 MMR系蛋白失表达及 MSI可能是子宫内膜非典型增生重要分子事件之一。