错配修复基因MLH1、MSH2、MSH6及PMS2在子宫内膜癌中的表达及临床意义

Expression of mismatch repair proteins( MLH1,MSH2,MSH6 and PMS2 ) in endometrial cancer and their clinical significance

目的探讨错配修复基因MLH1、MSH2、MSH6及PMS2在子宫内膜癌组织中的表达及临床意义。方法选取解放军总医院病理科2007—2016年间420例确诊为子宫内膜癌连续性病例为研究对象,采用免疫组织化学的方法对其中四种错配修复基因的表达进行检测及分析。结果 420例子宫内膜癌中四种错配修复基因MLH1、MSH2、MSH6、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),总的蛋白缺失率为34.5%(145/420)。在子宫内膜样癌中MMR蛋白缺失率为32.4%(125/386),其中低分化子宫内膜样癌中MMR蛋白缺失率为54.2%(32/59),且单个MMR蛋白在不同分化的子宫内膜样癌中的表达缺失率差异显著(P<0.05);非子宫内膜样癌中MMR蛋白缺失率为59%(20/34),与子宫内膜样癌相比较,发现MMR总蛋白及单个PMS2蛋白缺失率在两者间的差异性显著(P<0.05)。在FIGO分期中,单个MSH2蛋白在Ⅲ期中表达缺失率达18.6%且差异性显著(P<0.05)。MMR蛋白在黏膜内浸润、浅肌层及深肌层浸润中的表达缺失率分别为35%(14/40)、31%(92/299)、48.1%(39/81),不同浸润深度的子宫内膜癌中MMR蛋白缺失率差异性显著(P<0.05)。49例淋巴结转移的子宫内膜癌中有24例出现MMR蛋白缺失(P<0.05)。结论 MMR蛋白在低分化子宫内膜样癌、高FIGO分期、深肌层浸润及有淋巴结转移的子宫内膜癌中表达缺失率高且差异性显著。此结果表明,MMR蛋白的异常表达在子宫内膜癌的发生发展过程中起着重要作用,并提示患者预后不良,有效指导临床治疗和追踪,降低患者及其家族成员的癌症发病风险。

Objective To explore the expression and clinical significance of mismatch repair proteins（ MLH1,MSH2,MSH6 and PMS2） in endometrial cancer（ EC）. Methods A total of 420 cases with EC diagnosed by the surgical pathology examination from the Department of Pathology,PLA General Hospital,and the MLH1,MSH2,MSH6 and PMS2 proteins in EC were detected by immunohistochemistry. Results In the 420 tumor tissues,the expression loss rates of MLH1,MSH2,MSH6 and PMS2 protein were 17. 1%（ 72/420）,8. 1%（ 34/420）,7. 4%（ 31/420） and 26. 2%（ 110/420）,respectively; the total expression loss rate of four MMR protein was 34. 5%（ 145/420）. The expression loss rate of MMR protein was 32. 4% in the endometrioid adenocarcinoma,of which the expression loss rate of MMR protein was54. 2% in the poorly differentiated endometrioid adenocarcinoma,and the expression loss rate of every MMR protein in the different differentiated endometrioid adenocarcinoma had statistically significance（ P 〈0. 05）. The expression loss rate of MMR protein was 59% in the non-endometrioid adenocarcinoma,and the expression loss rate of MMR and PMS2 proteins had statistically significance compared to that of endometrioid adenocarcinoma（ P 〈0. 05）. The expression loss rate of MSH2 protein was 18. 6% in the FIGO staging Ⅲ（ P 〈0. 05）. The expression loss rate of MMR protein in the endometrial cancer with mucosal,superficial muscle invasion and deep muscle invasion were 35%（ 14/40）,31%（ 92/299） and 48. 1%（ 39/81） with statistical significance（ P 〈0. 05）. There were 24 patients with the expression loss rate of MMR protein in the 49 endometrial cancer patients with lymph node metastasis（ P 〈0. 05）. Conclusions The expression loss rate of MMR protein is high in poorly differentiated endometrioid adenocarcinoma,FIGO staging Ⅲ,deep myometrial invasion and lymph node metastasis of endometrial cancer cases. MMR protein plays an important role in the development of endometrial cancer and indicates poor prognosis. The data of this study can effectively guide the clinical treatment and follow-up,and reduce the risk of cancer in patients and their family members.