Analysis of microsatellite instability in endometroid carcinoma with deficient mismatch repair
10.3760/cma.j.cn112151-20210201-00114
- VernacularTitle:错配修复缺陷的子宫内膜样腺癌中微卫星不稳定性分析
- Author:
Yuhan ZHANG
1
;
Huanwen WU
;
Jing WANG
;
Zhiyong LIANG
Author Information
1. 中国医学科学院 北京协和医学院 北京协和医院病理科 100730
- Keywords:
Uterine neoplasms;
DNA mismatch repair;
Microsatellite instability;
Immunohistochemistry;
High-throughput nucleotide sequencing
- From:
Chinese Journal of Pathology
2021;50(5):470-475
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the microsatellite instability (MSI) status in endometrioid endometrial carcinoma (EEC) with deficient mismatch repair (dMMR) and to explore the concordance between MSI next generation sequencing (NGS)/PCR and MMR immunohistochemistry (IHC) results.Methods:Sixty dMMR EEC cases by IHC from November 2017 to February 2019 were selected in the Department of Pathology, Peking Union Medical College Hospital. Two pathologists reviewed the IHC results. The MSI status and the germline/somatic mutational status of MMR genes were analyzed by NGS. MLH1 promoter methylation status was determined by methylation-specific PCR (MSP) in cases with MLH1 protein deficiency. In cases with discrepant results between MMR IHC and MSI NGS, the MSI status was detected again by PCR, and the reasons for the discrepancy were discussed with gene mutation and MLH1 promoter methylation results.Results:Among 60 dMMR EEC specimens, 3 samples were re-assigned as proficient mismatch repair (pMMR) after pathological review, and identified as MSS by NGS. Another 3 dMMR cases showed MSI-uncertainty (MSI-U) by NGS due to insufficient tumor content. In the remaining 54 cases, the concordance between MMR IHC and MSI NGS was 87% (47/54). The seven discrepant cases was further analyzed: in 5 discrepant cases with MLH1/PMS2 protein loss, one case did not have enough samples for detection, one case was MSI-H, and the remaining three cases were MSS by PCR. All these 5 cases with MLH1/PMS2 protein loss showed the MLH1 promoter hypermethylation, two of which also had a somatic mutation in the MSH2 gene. The two discrepant cases with MSH6 protein loss were both MSS by PCR, one of which was considered to have Lynch syndrome with germline mutation in MSH6 gene.Conclusions:Although the overwhelming majority of dMMR EEC cases by IHC shows MSI-H by NGS/PCR, there are uncommon discrepant dMMR EEC cases with MSS. They are mostly found in cases with MLH1/PMS2 protein loss caused by MLH1 promoter hypermethylation and rarely related to Lynch syndrome. Both MMR IHC and MSI NGS/PCR tests have their advantages and disadvantages, complimentary to each other.
