MMR蛋白在515例子宫内膜样腺癌中表达及其与临床病理学特征的相关性分析

武全; 郭静伟; 雷雨馨; 胡晓儒; 王哲

doi:10.19401/j.cnki.1007-3639.2022.12.007

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MMR蛋白在515例子宫内膜样腺癌中表达及其与临床病理学特征的相关性分析

论著 | 更新时间：2025-12-31

- MMR蛋白在515例子宫内膜样腺癌中表达及其与临床病理学特征的相关性分析
- Expression of MMR in 515 cases of endometrioid adenocarcinoma and its correlation with clinicopathological features
- 中国癌症杂志 2022年32卷第12期页码：1190-1198
- 作者机构：
  
  中国医科大学附属盛京医院病理科，辽宁沈阳 110000
- 作者简介：
  
  [ "武全（ORCID:0000-0003-0289-7344），硕士。" ]
  王哲（ORCID:0000-0001-6951-071X），博士，副教授。
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.12.007
  中图分类号： R737.33
- 收稿：2022-05-13，
  
  修回：2022-11-08，
  
  纸质出版：2022-12-30
- 稿件说明：
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武全, 郭静伟, 雷雨馨, 等. MMR蛋白在515例子宫内膜样腺癌中表达及其与临床病理学特征的相关性分析[J]. 中国癌症杂志, 2022,32(12):1190-1198.

Quan WU, Jingwei GUO, Yuxin LEI, et al. Expression of MMR in 515 cases of endometrioid adenocarcinoma and its correlation with clinicopathological features[J]. China Oncology, 2022, 32(12): 1190-1198.
武全, 郭静伟, 雷雨馨, 等. MMR蛋白在515例子宫内膜样腺癌中表达及其与临床病理学特征的相关性分析[J]. 中国癌症杂志, 2022,32(12):1190-1198. DOI： 10.19401/j.cnki.1007-3639.2022.12.007.

Quan WU, Jingwei GUO, Yuxin LEI, et al. Expression of MMR in 515 cases of endometrioid adenocarcinoma and its correlation with clinicopathological features[J]. China Oncology, 2022, 32(12): 1190-1198. DOI： 10.19401/j.cnki.1007-3639.2022.12.007.

摘要

背景与目的：

林奇综合征（Lynch syndrome，LS）相关的子宫内膜癌有着独特的临床病理学特征及治疗手段。对新发子宫内膜癌患者采用免疫组织化学（immunohistochemistry，IHC）染色的方法检测错配修复（mismatch repair，MMR）蛋白表达情况，可以有效地筛查LS相关的癌症患者。本研究探讨MMR蛋白（MLH1、MSH2、MSH6及PMS2）在子宫内膜样腺癌中的表达情况及其与患者临床病理学特征的关系。

方法：

收集中国医科大学盛京医院2018年1月—2020年8月共515例子宫内膜样腺癌连续性病例为研究对象，年龄范围为28 ~ 81（57.73±8.41）岁。采用IHC染色的方法检测癌组织中MLH1、MSH2、MSH6和PMS2蛋白表达情况，应用聚合酶链式反应（polymerase ch

ain reaction，PCR）方法对MLH1蛋白表达缺失的标本进行基因的甲基化检测，并且分析MMR蛋白表达缺失情况与子宫内膜样腺癌临床病理学特征的关系。只要有一种MMR蛋白表达缺失即判定为MMR蛋白错配修复缺陷（deficient mismatch repair，dMMR），蛋白全部阳性则判定为MMR表达完整（proficient mismatch repair，pMMR）。

结果：

515例子宫内膜样腺癌中有138例（26.8%）发生MMR蛋白表达缺失，MLH1、PMS2、MSH2及MSH6蛋白表达缺失率分别是16.3%（84/515）、19.0%（98/515）、5.4%（28/515）、8.0%（41/515）。MMR蛋白的缺失以MLH1和PMS2联合表达缺失（60.9%，84/138）为主；其次为MSH2和MSH6联合表达缺失（18.8%，26/138）；MSH2、MSH6和PMS2联合表达缺失有2例（1.4%，2/138）；PMS2、MSH2和MSH6蛋白单独表达缺失比例分别为8.0%（11/138）、1.4%（2/138）、10.1%（14/138）。对27例MLH1蛋白表达缺失标本进行甲基化检测，结果显示，阳性率为85.2%（23/27）。515例子宫内膜样腺癌组织中的MMR蛋白表达缺失与患者发病年龄、国际妇产科联合会（The International Federation of Gynecology and Obstetrics，FIGO）分期、组织学分化程度、浸润深度、脉管转移、神经侵犯、淋巴结转移、p53异常表达、肿瘤浸润淋巴细胞（tumor infiltrating lymphocyte，TIL）及肿瘤伴瘤周淋巴细胞有相关性，而与是否累及子宫下段无关。与pMMR的患者相比，dMMR的患者发病年龄更小，FIGO临床分期多为Ⅲ ~ Ⅳ期，组织学分化程度多为低分化，肿瘤多无肌层浸润，肿瘤多出现脉管神经侵犯及淋巴结转移，肿瘤浸润淋巴细胞增多，且肿瘤伴瘤周淋巴细胞更显著，MSH6蛋白缺失患者多无p53异常表达。

结论：

dMMR的子宫内膜样腺癌患者具有独特的临床病理学特征。应用免疫组织化学染色方法检测MMR蛋白表达情况，并对MLH1表达缺失的标本进行基因甲基化检测，能初步筛查LS患者，对肿瘤患者免疫治疗具有一定指导意义。

Abstract

Background and purpose:

Lynch syndrome associated endometrial carcinoma has unique clinicopathological features and treatment methods. The detection of mismatch repair (MMR) protein expression by immunohistochemical (IHC) staining in patients with newly diagnosed endometrial cancer can effectively screen patients with Lynch syndrome associated cancer. This study investigated the expression of mismatch repair proteins (MLH1

MSH2

MSH6 and PMS2) in endometrioid adenocarcinoma and its relationship with clinicopathological features.

Methods:

A total of 515 cases of endometrioid adenocarcinoma were collected from Shengjing Hospital of China Medical University from January 2018 to August 2020.The patients were 28 to 81 (57.73 ± 8.41) years old. IHC method was used to detect the protein expressions of MLH1

MSH2

MSH6 and PMS2 in cancer tissues. Polymerase chain reaction (PCR) was used to detect the gene methylation o

f MLH1 protein expression deficient specimens

and the relationship between MMR protein expression deletion and clinicopathological features of endometrioid adenocarcinoma was analyzed. As long as there was a loss of MMR protein expression

it was judged as deficient mismatch repair (dMMR). If all MMR proteins were positive

it was judged as proficient mismatch repair (pMMR).

Results:

MMR protein was absent in 138 (26.8%) of 515 cases of endometrioid adenocarcinoma. The deletion rates of MLH1

PMS2

MSH2 and MSH6 proteins were 16.3% (84/515)

19.0% (98/515)

5.4% (28/515) and 8.0% (41/515)

respectively. The loss of MMR protein expression was mainly the combined loss of MLH1 and PMS2 expressions (60.9%

84/138)

and the second was the combined deletion of MSH2 and MSH6 expressions (18.8%

26/138). There were 2 cases of combined deletion of MSH2

MSH6 and PMS2 expressions (1.4%

2/138). The single deletion rates of PMS2

MSH2 and MSH6 proteins were 8.0% (11/138)

1.4% (2/138) and 10.1% (14/138)

respectively. MLH1 protein expression deletion was detected in 27 samples

and the results showed that the methylation positive rate was 85.2% (23/27). The loss of MMR protein expression in 515 cases of endometrioid adenocarcinoma was correlated with the age of onset

the International Federation of Gynecology and Obstetrics (FIGO) stage

the degree of histological differentiation

depth of invasion

vascular metastasis

nerve invasion

lymph node metastasis

abnormal expression of p53

tumor infiltrating lymphocytes and tumor with peritumoral lymphocyte infiltration. MMR protein status was not correlated with lower uterine segment involvement. Compared with pMMR patients

the onset age of dMMR was younger

and FIGO stage was mostly stage Ⅲ-Ⅳ. The histological differentiation degree was mostly low

most tumors had no myometrial infiltration

and most tumors had vascular metastasis

nerve invasion and lymph node metastasis. The lymphocyte infiltration in the tumor with dMMR was increased

and the tumor with per

itumoral lymphocyte was more significant. Most patients with MSH6 protein deficiency had no abnormal expression of p53.

Conclusion:

Compared with pMMR patients

dMMR patients in Northeast China has unique clinicopathological characteristics. Detecting the expression of MMR protein by immunohistochemical staining and detection of the gene methylation of MLH1 expression deficient specimens can preliminarily screen patients with Lynch syndrome

which has certain guiding significance for immunotherapy of tumor patients.

关键词

Keywords

references

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