Jin W, Wang L Q, Liu Y, Liu A J
Department of Pathology, General Hospital of PLA, Beijing 100853, China.
Zhonghua Fu Chan Ke Za Zhi. 2018 Dec 25;53(12):823-830. doi: 10.3760/cma.j.issn.0529-567x.2018.12.005.
To explore the expression and clinical significance of mismatch repair (MMR) protein and MLH1 promoter methylation testing in endometrial cancer (EC) . A total of 420 cases with EC diagnosed by the surgical pathology examination from the Department of Pathology of PLA General Hospital, MLH1, MSH2, MSH6 and PMS2 protein in EC were detected by immunohistochemistry and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) testing. (1) Of the 420 tumor cases, the total expression loss rate of MMR protein was 34.5% (145/420) , the expression loss rates of MLH1, MSH2, MSH6 and PMS2 protein were respectively 17.1% (72/420) , 8.1% (34/420) , 7.4% (31/420) , 26.2% (110/420) and loss rates of MLH1 and PMS2, MSH2 and MSH6 were16.7% (70/420) , 6.2% (26/420). When there was a loss of MMR protein expression, any one or more protein expression deletions in MLH1, PMS2, MSH2 and MSH6, it could be Lynch syndrome related endometrial carcinoma (LS-EC). The expression loss rate of MMR protein in the poorly differentiated endometrioid adenocarcinoma was higher than that in the well differentiated endometrioid adenocarcinoma (0.05). (2) The expression loss rate of MMR and PMS2 protein had statistically significant between the endometrioid adenocarcinoma and non-endometrioid adenocarcinoma (0.01). The expression loss rate of MSH2 protein had statistically significant in the stage Ⅲ (0.01). Moreover, there were also significant differences in depth of myometrial invasion and lymph node metastasis between the expression loss rate of MMR protein (0.05). (3) The expression loss rate of MLH1 protein was 72 cases and 57 cases had MLH1 promoter methylation testing (excluding those who were not qualified for DNA testing). The positive rate was 47.4% (27/57). Therefore, these patients were sporadic endometrial cancer, not non-LS-EC. MMR protein may be play an important role in the development of endometrial cancer and be indicated poor prognosis. Immunohistochemical staining and MLH1 promoter methylation detection may be play an important role in the screening of the LS-EC.
探讨错配修复(MMR)蛋白表达及MLH1启动子甲基化检测在子宫内膜癌(EC)中的表达情况及临床意义。收集解放军总医院病理科手术病理确诊的EC患者420例,采用免疫组化及甲基化特异性多重连接依赖探针扩增(MS-MLPA)技术检测EC组织中MLH1、MSH2、MSH6和PMS2蛋白表达情况。(1)420例肿瘤患者中,MMR蛋白总缺失率为34.5%(145/420),MLH1、MSH2、MSH6和PMS2蛋白缺失率分别为17.1%(72/420)、8.1%(34/420)、7.4%(31/420)、26.2%(110/420),MLH1与PMS2、MSH2与MSH6同时缺失率分别为16.7%(70/420)、6.2%(26/420)。MMR蛋白表达缺失时,MLH1、PMS2、MSH2和MSH6中任意一种或多种蛋白表达缺失,可能为林奇综合征相关子宫内膜癌(LS-EC)。低分化子宫内膜样腺癌MMR蛋白缺失率高于高分化子宫内膜样腺癌(P<0.05)。(2)子宫内膜样腺癌与非子宫内膜样腺癌MMR及PMS2蛋白表达缺失率差异有统计学意义(P<0.01)。MSH2蛋白表达缺失率在Ⅲ期差异有统计学意义(P<0.01)。MMR蛋白表达缺失率在肌层浸润深度及淋巴结转移方面差异也有统计学意义(P<0.05)。(3)MLH1蛋白表达缺失72例,其中57例进行MLH1启动子甲基化检测(排除DNA检测不合格者),阳性率为47.4%(27/57)。因此,这些患者为散发性子宫内膜癌,而非非LS-EC。MMR蛋白可能在子宫内膜癌发生发展中起重要作用,提示预后不良。免疫组化染色及MLH1启动子甲基化检测可能在LS-EC筛查中起重要作用。