Wang C S, Zhang B, Sun Q, Yang J, Cui X B, Wu H Y
Department of Pathology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
Zhonghua Bing Li Xue Za Zhi. 2025 Feb 8;54(2):126-134. doi: 10.3760/cma.j.cn112151-20240531-00354.
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. A retrospective analysis was conducted with summary of immunohistochemical data from 7 867 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. The Cohen κ values 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 7 867 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. 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.
为研究两种标志物PMS2和MSH6（2-MMR）的免疫组化结果能否替代四种标志物MLH1、PMS2、MSH2和MSH6（4-MMR）来检测错配修复缺陷（dMMR）癌症。对2018年3月至2023年3月期间中国南京南京大学医学院附属鼓楼医院7867例胃癌、结直肠癌、子宫内膜癌及其他疾病的免疫组化数据进行回顾性分析并总结。检测2-MMR和4-MMR结果的一致性。对具有特定表型的患者进行微卫星不稳定性（MSI）和二代测序（NGS）检测。2-MMR和4-MMR在胃癌、结直肠癌、子宫内膜癌及其他疾病中的Cohen κ值分别为0.88、0.99、0.88和1.00。总体一致性、敏感性和特异性分别为0.97、99.6%和100.0%。2-MMR和4-MMR均可检测出不同临床病理特征之间的差异。7867例患者中有24例（0.3%）具有MMR特殊表型，其中6例被选进行MSI和NGS分子检测。MSI分析显示所有病例均为MSI-H，而NGS发现其中5例有MMR相关基因突变，1例有POLE p.S297F突变。与4-MMR相比，2-MMR具有较高的一致性、特异性和敏感性。特殊表型病例仅占极低比例。因此，在dMMR筛查中4-MMR可能可用2-MMR替代。
