PMS2和MSH6双抗体检测在肿瘤错配修复缺陷筛查中的运用  

Application of PMS2 and MSH6 double-antibody detection in screening of mismatch repair deficient tumors

作　　者：王朝姗 张标[1] 孙琦[1] 杨军[1] 崔晓宾 吴鸿雁[1] Wang Chaoshan;Zhang Biao;Sun Qi;Yang Jun;Cui Xiaobin;Wu Hongyan(Department of Pathology,the Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院病理科,南京210008

出　　处：《中华病理学杂志》2025年第2期126-134,共9页Chinese Journal of Pathology

摘　　要：目的探讨检测2个标志物PMS2、MSH6(以下简称2-MMR)的免疫组织化学结果能否替代4个标志物MLH1、PMS2、MSH2、MSH6(以下简称4-MMR)来揭示该样本是否有错配修复缺陷(mismatch repair deficient,dMMR)。方法对南京大学医学院附属鼓楼医院2018年3月至2023年3月诊断的7867例胃癌、结直肠癌、子宫内膜癌及其他疾病的免疫组织化学数据进行回顾性分析汇总,对比2-MMR与4-MMR的一致性。并且对特殊表型病例进行微卫星不稳定性(MSI)检测和二代测序检测。结果在胃癌、结直肠癌、子宫内膜癌和其他疾病中2-MMR与4-MMR检测的一致性Cohenκ值分别为0.88、0.99、0.88和1.00,总体一致性为0.97,灵敏度为99.6%,特异度为100.0%。2-MMR与4-MMR检测均能体现不同临床病理特征之间的差异。7867例患者中出现24例MMR特殊表型病例(0.3%,24/7867),研究选取其中6例进行MSI和二代测序分子检测,MSI检测结果均为高频MSI,二代测序检测发现其中5例有MMR相关基因突变,1例有POLE p.S297F突变。结论2-MMR与4-MMR免疫组织化学检测相比,具有高一致性、特异度和灵敏度,特殊表型病例占比极低,因此在筛查dMMR方面可考虑采用2-MMR取代4-MMR。Objective To investigate whether the immunohistochemical results of two markers PMS2 and MSH6(2-MMR)could replace the four markers MLH1,PMS2,MSH2 and MSH6(4-MMR)to detect mismatch repair deficient(dMMR)cancers.Methods A retrospective analysis was conducted with summary of immunohistochemical data from 7867 cases of gastric cancer,colorectal cancer,endometrial cancer,and other diseases in the Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing,China,from March 2018 to March 2023.The consistency of 2-MMR and 4-MMR results was examined.Microsatellite instability(MSI)and next-generation sequencing(NGS)were performed in patients with specific phenotypes.Results The Cohenκvalues of 2-MMR and 4-MMR in gastric cancer,colorectal cancer,endometrial cancer and other diseases were 0.88,0.99,0.88 and 1.00,respectively.The overall consistency,sensitivity and specificity were 0.97,99.6%,and 100.0%,respectively.Both 2-MMR and 4-MMR could detect the difference between various clinicopathological features.24(0.3%)of the 7867 patients were found to have a special phenotype of MMR,and 6 of them were selected for MSI and NGS molecular testing.MSI analysis showed MSI-H in all cases,while NGS found that 5 of them had MMR-related gene mutations and 1 had POLE p.S297F mutation.Conclusions Compared with 4-MMR,2-MMR has high consistency,specificity and sensitivity.The cases with special phenotype only account for extremely low proportion.Therefore,4-MMR may be replaced with 2-MMR in dMMR screening.

关 键 词：DNA错配修复 免疫组织化学 微卫星不稳定性 PMS2 MSH6 

分 类 号：R730.43[医药卫生—肿瘤]