{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:12:43Z","timestamp":1786990363745,"version":"build-2736575974"},"reference-count":52,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Objectives<\/jats:title>\n               <jats:p>Identification of endometrial cancers (EC) with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) is essential for Lynch syndrome screening and treatment stratification. We aimed to assess the utility of immunohistochemistry (IHC) staining for MMR protein expression and polymerase chain reaction (PCR)-based MSI assays in EC and the correlation between MMR\/MSI status and various clinicopathological parameters.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Methods<\/jats:title>\n               <jats:p>We reviewed the clinical and pathological information of 333 patients with EC. MMR protein expression was assessed as retained or lost to determine MMR status by IHC staining, and MSI status was identified by PCR capillary electrophoresis (PCR-CE) testing with a National Cancer Institute (NCI) panel. The correlation of MMR\/MSI status with clinicopathological features was determined by statistical analysis. Discrepant results were further analyzed using an alternative PCR-CE MSI (Promega panel) method, MLH1 promoter methylation assays, and next-generation sequencing (NGS).<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>Among the EC patients, the overall percentage of dMMR was 25.2%, and the overall percentage of MSI-H was 24%. Among the dMMR patients, 50 (59.5%) showed loss of MLH1 and PMS2 expression, 19 (22.6%) loss of MSH2 and MSH6 expression, and seven (8.3%) and eight (9.5%) loss of PMS2 and MSH6 expression, respectively. The dMMR subgroup was significantly younger than the pMMR subgroup, especially for &lt;60-years-old patients (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.038). In addition, we identified a strong correlation between MMR\/MSI status and high-grade endometrioid or nonendometrioid components (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.004 or <jats:italic>p<\/jats:italic>\u00a0=\u00a00.003). IHC staining and PCR-CE assay results showed a high level of overall concordance (98.8%, Cohen\u2019s <jats:italic>\u03ba<\/jats:italic>\u00a0=\u00a00.98). Four patients were found to have dMRR\/MSS in both examinations. We reanalyzed them with additional methods. One case showed MLH1 promotor methylation, and the other three cases harbored MSH6 germline pathogenic variations. One of the cases with MSH6 deficiency was reanalyzed as MSI-H by alternative PCR-CE assay or NGS testing.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusions<\/jats:title>\n               <jats:p>This study indicates that the combined use of MMR-IHC and PCR-CE MSI analyses may effectively avoid misdiagnoses of EC patients with dMMR\/MSI-H. However, use of PCR-CE alone to evaluate MMR\/MSI status may lead to missed diagnosis, especially for EC patients with MSH6 deficiency and presenting MSS.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.15920","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T07:56:40Z","timestamp":1693209400000},"page":"e15920","source":"Crossref","is-referenced-by-count":10,"title":["A retrospective study of consistency between immunohistochemistry and polymerase chain reaction of microsatellite instability in endometrial cancer"],"prefix":"10.7717","volume":"11","author":[{"given":"Cheng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Ren","sequence":"additional","affiliation":[{"name":"West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanxin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongni","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"10.7717\/peerj.15920\/ref-1","doi-asserted-by":"publisher","first-page":"4479","DOI":"10.1002\/cam4.4832","article-title":"Simple IHC reveals complex MMR alternations than PCR assays: validation by LCM and next-generation sequencing","volume":"11","author":"Amemiya","year":"2022","journal-title":"Cancer Medicine"},{"key":"10.7717\/peerj.15920\/ref-2","doi-asserted-by":"publisher","first-page":"896","DOI":"10.6004\/jnccn.2019.0039","article-title":"NCCN guidelines 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