METHODS: To search for epigenetic events, methylation-specific multiplex ligation-dependent probe amplification was employed to compare the methylation status of 64 tissue samples with atypical endometrial hyperplasia, 60 tissue samples with endometrial hyperplasia without atypia, and 40 control tissue samples with normal endometrium.
RESULTS: Differences in DNA methylation among the groups were found in PTEN, CDH13, and MSH6 promoters (PTEN: atypical hyperplasia 32%, benign hyperplasia 6.8%, normal endometrium 10%; P=0.004; CDH13: atypical hyperplasia, 50%; benign hyperplasia, 43%; normal endometrium 8.1%; P=0.003; MSH6 atypical hyperplasia 84%, benign hyperplasia, 62%; normal endometrium, 52%; P=0.008.) Higher rates of CDH13 promoter methylation were identified in the groups with both forms of endometrial hyperplasia when compared to the control group (atypical hyperplasia, P=0.003, benign hyperplasia, P=0.0002). A higher rate of DNA methylation of the PTEN and MSH6 promoters was observed in samples with atypical endometrial hyperplasia than in samples with benign endometrial hyperplasia (PTEN: P=0.02; MSH6: P=0.01) and samples with normal endometrial tissue (PTEN, P=0.04; MSH6, P=0.006).
CONCLUSIONS: DNA methylation of CDH13, PTEN, and MSH6 appear to be involved in the development of endometrial hyperplasia.
方法:要搜索表观遗传事件,甲基化特异性多重连接依赖性探针扩增用于比较64个组织样本与非典型子宫内膜增生的甲基化状态,60个子宫内膜增生组织样本,无异型,和40个正常子宫内膜的对照组织样本。
结果:在PTEN中发现各组之间DNA甲基化的差异,CDH13和MSH6启动子(PTEN:非典型增生32%,良性增生6.8%,正常子宫内膜10%;P=0.004;CDH13:不典型增生,50%;良性增生,43%;正常子宫内膜8.1%;P=0.003;MSH6不典型增生84%,良性增生,62%;正常子宫内膜,52%;P=0.008。)与对照组相比,两种形式的子宫内膜增生组中CDH13启动子甲基化率较高(非典型增生,P=0.003,良性增生,P=0.0002)。在非典型子宫内膜增生的样品中观察到PTEN和MSH6启动子的DNA甲基化率高于良性子宫内膜增生的样品(PTEN:P=0.02;MSH6:P=0.01)和正常子宫内膜组织的样品(PTEN,P=0.04;MSH6,P=0.006)。
结论:CDH13,PTEN,MSH6似乎参与了子宫内膜增生的发生发展。