错配修复（ＭＭＲ）蛋白（ＭＬＨ１、ＰＭＳ２、ＭＳＨ２和ＭＳＨ６）表达与子宫内膜癌临床病理特征和预后相关性分析

黄金长 肖英 黄雪梅

[摘要] 目的 分析错配修复（MMR）蛋白表达与子宫内膜癌临床病理特征和预后相关性。 方法 选取我院2018年2月至2020年5月收治的70例子宫内膜癌（UCEC）患者，采用免疫组化法对4种蛋白（MLH1、PMS2、MSH2和MSH6）表达情况进行检测，并将4种MMR蛋白中1种及以上表达缺失判定为错配修复基因缺陷（dMMR），全部阳性则判定为错配修复基因完整（pMMR）。检测UCEC患者MMR蛋白缺失情况并对其与病理特征的关系进行分析。 结果 4种MMR蛋白表达均定位于肿瘤细胞核，可作为内对照;dMMR组与pMMR组年龄、病理组织学类型、临床分期及淋巴结转移等比较，差异有统计学意义（P<0.05），表现为dMMR组发病年龄低、肿瘤分期低、淋巴结转移少见。 结论 dMMR子宫内膜癌比例较低，且MLH1和PM52蛋白表达缺失与MSH2和MSH6相比较为多见。MLH1和PMS2、MSH2和MSH6常协同表达或缺失。MMR蛋白与UCEC临床病理特征关系密切。MMR蛋白对预测UCEC的恶性程度、临床预后及UCEC发病机制方面有指导意义。

[关键词] 子宫内膜癌;错配修复;免疫组化;病理特征

[Abstract] Objective To analyze the correlation between expressions of mismatch repair（MMR） proteins and clinicopathological features and prognosis of endometrial carcinoma. Methods A total of 70 patients with uterine corpus endometrial carcinoma（UCEC） admitted to our hospital from February 2018 to May 2020 were selected， and the expression of four types of MMR proteins was detected by immunohistochemistry. The loss of expression of one or more of the four types of MMR proteins（MLH1， PMS2， MSH2 and MSH6） was judged as different mismatch repair（dMMR） gene defect， and all positive MMR proteins were judged as a complete mismatch repair gene（pMMR）. The MMR protein deletion in patients with UCEC was detected and its relationship with pathological features was analyzed. Results The expression of four MMR proteins were located in tumor nuclei and could be used as internal control.There were statistically significant differences between the dMMR group and the pMMR group in onset age， histological type， clinical stage and lymph node metastasis， etc，the difference was statistically significant（P<0.05）. In the dMMR group，the age of onset was low， the stage of tumor was low， and lymph node metastasis was rare. Conclusion The rate of endometrial carcinoma in dMMR is low， and the loss of MLH1 and PM52 protein expression is more common than MSH2 and MSH6.The MLH1 and PMS2， MSH2 and MSH6 are often co-expressed or absent. MMR protein is closely related to the clinicopathological features of UCEC. MMR protein has guiding significance in aspects of predicting the malignant degree， clinical prognosis and pathogenesis of UCEC.

[Key words] Endometrial carcinoma; Mismatch repair; Immunohistochemistry; Pathological features

子官內膜样腺癌中的错配修复（Mismatch repair，MMR）蛋白缺陷患者具有一些显著不同于传统Ⅰ型与Ⅱ型癌的特征，肿瘤具有显著的宿主炎症反应，主要表现为肿瘤周围淋巴细胞及肿瘤浸润淋巴细胞炎症，伴微囊性、伸长及碎片状（Microcystic，elongated and fragmented，MELF）浸润方式。子宫内膜样腺癌通常伴有纤维黏液样间质或富含炎性细胞间质：特殊的病理形态常具有隐弊性。两者在病理形态上有一定的相似性，且伴MELF浸润的子宫内膜样腺癌与错配修复蛋白表达缺失均与FIGO分期、子宫深肌层浸润、淋巴结转移率高及淋巴管血管侵犯相关[1-2]。本研究采用免疫组化法对（Uterine corpus endometrial carcinoma，UCEC）患者标本进行MMR蛋白MLH1、MSH2、MSH6及PMS2检测，并对其与临床特征的关系进行分析，现报道如下。

1 资料与方法

1.1 一般资料

选取我院2018年2月至2020年5月收治的70例子宫内膜癌（Uterine corpus endometrial carcinoma，UCEC）患者，年龄53～76岁，平均（64.59±3.28）岁。所有患者均行病理学活检切片检查，并经两位资深病理医师进行诊断。……