{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T08:56:15Z","timestamp":1774601775689,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008376","name":"Helsingin ja Uudenmaan Sairaanhoitopiiri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008376","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mismatch repair (MMR) system has been implicated in the response of mammalian cells to ionizing radiation and DNA damaging agents. We investigated the value of the MMR system in predicting response to adjuvant therapy in endometrial cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a single institution retrospective study. MMR protein status of endometrial carcinomas was assessed by immunohistochemistry. MMR deficient (MMR\u2010D) tumors were identified as <jats:italic>MLH1<\/jats:italic> methylated or nonmethylated by methylation\u2010specific multiplex ligation\u2010dependent probe amplification. Tumors with abnormal p53 staining or <jats:italic>polymerase \u03f5<\/jats:italic> exonuclease domain mutation were excluded from the MMR proficient subgroup, which was termed as \u201cno specific molecular profile\u201d (NSMP). Disease\u2010specific survival analyses were adjusted for age, stage, histology and grade, depth of myometrial invasion, and lymphovascular space invasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 505 patients were included in the study. Median follow\u2010up time was 81\u00a0months (range 1\u2013136). Whole pelvic radiotherapy (adjusted hazard ratio [HR] 0.092 vs. no adjuvant therapy) and chemotherapy combined with radiotherapy (adjusted HR 0.18) were associated with improved disease\u2010specific survival in the NSMP subgroup (n\u00a0=\u00a0218). In contrast, adjuvant therapies showed no effect on disease\u2010specific survival in the full MMR\u2010D cohort (n\u00a0=\u00a0287) or in <jats:italic>MLH1<\/jats:italic> methylated tumors (n\u00a0=\u00a0154). Whole pelvic radiotherapy (adjusted HR 25 vs. no adjuvant therapy\/vaginal brachytherapy) and chemotherapy combined with whole pelvic radiotherapy (adjusted HR 32) were associated with poor disease\u2010specific survival in MMR\u2010D nonmethylated tumors (n\u00a0=\u00a070).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MMR protein and <jats:italic>MLH1<\/jats:italic> methylation status predict the response to adjuvant therapy in endometrial cancer. The MMR system could be utilized for selection of patients who most likely benefit from adjuvant therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.3691","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T23:56:55Z","timestamp":1610755015000},"page":"1034-1042","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Mismatch repair protein and <i>MLH1<\/i> methylation status as predictors of response to adjuvant therapy in endometrial cancer"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4372-2367","authenticated-orcid":false,"given":"Mikko","family":"Loukovaara","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Helsinki University Hospital and University of Helsinki Helsinki 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