{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:49:06Z","timestamp":1785905346416,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Mismatch repair deficiency (MMRd) is a critical biomarker in endometrial cancer (EC) for prognostication, Lynch syndrome screening, and immunotherapy eligibility. This study aimed to determine the prevalence of MMRd and its correlation with clinicopathological characteristics in EC. This prospective observational cohort included 93 patients with EC undergoing primary surgical treatment, managed as per the European Society of Gynaecological Oncology (ESGO) guidelines. MLH1, PMS2, MSH2, and MSH6 expression was assessed through immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded hysterectomy specimens. Associations between mismatch repair (MMR) status and histology, grade, lymphovascular space invasion (LVSI), myometrial invasion, FIGO 2023 stage, nodal status, recurrence, and survival were analyzed. The median age was 66 years. Most tumors were endometrioid (86%), 29% were grade 3, 45.2% showed deep myometrial invasion, and 23.7% had substantial LVSI. MMRd was identified in 41.9% of cases, with MLH1 and PMS2 loss being most frequent, and was significantly associated with endometrioid histology (p = 0.027) and deep myometrial invasion (p = 0.011). No significant correlations were found with grade, LVSI, FIGO stage, nodal involvement, recurrence, or overall survival. Routine MMR assessment may refine risk stratification and guide individualized treatment decisions.<\/jats:p>","DOI":"10.3390\/ijms27156877","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence of Mismatch Repair Deficiency and Its Association with Histopathological Parameters in Endometrial Cancer: A Prospective Cohort Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-0143","authenticated-orcid":false,"given":"Emmanouela-Aliki","family":"Almperi","sequence":"first","affiliation":[{"name":"Gynaecologic Oncology Unit, 2nd Department of Obstetrics and Gynaeocology, Aristotle University of Thessaloniki, 54622 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrysoula","family":"Margioula-Siarkou","sequence":"additional","affiliation":[{"name":"Gynaecologic Oncology Unit, 2nd Department of Obstetrics and Gynaeocology, Aristotle University of Thessaloniki, 54622 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristarchos","family":"Almperis","sequence":"additional","affiliation":[{"name":"Gynaecologic Oncology Unit, 2nd Department of Obstetrics and Gynaeocology, Aristotle University of Thessaloniki, 54622 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor A.","family":"Zwimpfer","sequence":"additional","affiliation":[{"name":"Gynecological Cancer Centre, University Hospital Basel, University of Basel, 4031 Basel, Switzerland"},{"name":"Department of Biomedicine, University of Basel, 4031 Basel, Switzerland"},{"name":"Cancer Research, Peter MacCallum Cancer Center, East Melbourne, VIC 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Daponte","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Medical School, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikoletta","family":"Daponte","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Medical School, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6347-7223","authenticated-orcid":false,"given":"Thomas","family":"Vrekoussis","sequence":"additional","affiliation":[{"name":"Laboratory of Human Reproduction, Department of Obstetrics and Gynecology, Medical School, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-5407","authenticated-orcid":false,"given":"Theodora","family":"Papamitsou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7144-2840","authenticated-orcid":false,"given":"Konstantinos","family":"Dinas","sequence":"additional","affiliation":[{"name":"Gynaecologic Oncology Unit, 2nd Department of Obstetrics and Gynaeocology, Aristotle University of Thessaloniki, 54622 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5564-0406","authenticated-orcid":false,"given":"Stamatios","family":"Petousis","sequence":"additional","affiliation":[{"name":"Gynaecologic Oncology Unit, 2nd Department of Obstetrics and Gynaeocology, Aristotle University of Thessaloniki, 54622 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer Statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network, and Levine, D.A. (2013). Integrated Genomic Characterization of Endometrial Carcinoma. Nature, 497, 67\u201373. Erratum in Nature 2013, 500, 242.","DOI":"10.1038\/nature12113"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1136\/ijgc-2020-002230","article-title":"ESGO\/ESTRO\/ESP Guidelines for the Management of Patients with Endometrial Carcinoma","volume":"31","author":"Concin","year":"2021","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.4132\/jptm.2021.02.19","article-title":"Mismatch Repair Deficiency and Clinicopathological Characteristics in Endometrial Carcinoma: A Systematic Review and Meta-Analysis","volume":"55","author":"Jumaah","year":"2021","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Santoro, A., Angelico, G., Travaglino, A., Inzani, F., Arciuolo, D., Valente, M., D\u2019Alessandris, N., Scaglione, G., Fiorentino, V., and Raffone, A. (2021). New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO\/ESTRO\/ESP Guidelines. Cancers, 13.","DOI":"10.3390\/cancers13112623"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6870","DOI":"10.1073\/pnas.95.12.6870","article-title":"Incidence and Functional Consequences of hMLH1 Promoter Hypermethylation in Colorectal Carcinoma","volume":"95","author":"Herman","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s10689-007-9145-9","article-title":"The Biochemical Basis of Microsatellite Instability and Abnormal Immunohistochemistry and Clinical Behavior in Lynch Syndrome: From Bench to Bedside","volume":"7","author":"Boland","year":"2008","journal-title":"Fam. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1038\/s41436-019-0536-8","article-title":"The Proportion of Endometrial Cancers Associated with Lynch Syndrome: A Systematic Review of the Literature and Meta-Analysis","volume":"21","author":"Ryan","year":"2019","journal-title":"Genet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/ng.283","article-title":"Heritable Somatic Methylation and Inactivation of MSH2 in Families with Lynch Syndrome Due to Deletion of the 3\u2032 Exons of TACSTD1","volume":"41","author":"Ligtenberg","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1093\/annonc\/mdz116","article-title":"ESMO Recommendations on Microsatellite Instability Testing for Immunotherapy in Cancer, and Its Relationship with PD-1\/PD-L1 Expression and Tumour Mutational Burden: A Systematic Review-Based Approach","volume":"30","author":"Luchini","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.3332\/ecancer.2020.1061","article-title":"Clinicopathologic Features of Endometrial Cancer with Mismatch Repair Deficiency","volume":"14","author":"Gordhandas","year":"2020","journal-title":"Ecancermedicalscience"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.dnarep.2015.11.019","article-title":"DNA Mismatch Repair and the DNA Damage Response","volume":"38","author":"Li","year":"2016","journal-title":"DNA Repair"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.tjog.2023.07.015","article-title":"Clinicopathologic Significance of Mismatch Repair Protein Expression in Endometrioid Endometrial Cancer","volume":"62","author":"Kim","year":"2023","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.7150\/jca.112935","article-title":"Mismatch Repair Protein Deficiency and Its Relationship with Clinicopathological Factors in Endometrial Cancer: A Retrospective Study","volume":"16","author":"Aytekin","year":"2025","journal-title":"J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e15920","DOI":"10.7717\/peerj.15920","article-title":"A Retrospective Study of Consistency between Immunohistochemistry and Polymerase Chain Reaction of Microsatellite Instability in Endometrial Cancer","volume":"11","author":"Wang","year":"2023","journal-title":"PeerJ"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3802\/jgo.2015.26.1.40","article-title":"DNA Mismatch Repair-Related Protein Loss as a Prognostic Factor in Endometrial Cancers","volume":"26","author":"Kato","year":"2015","journal-title":"J. Gynecol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ygyno.2019.08.019","article-title":"TCGA Molecular Groups of Endometrial Cancer: Pooled Data about Prognosis","volume":"155","author":"Raffone","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/s41379-020-0501-8","article-title":"Clinicopathological Significance of Deficient DNA Mismatch Repair and MLH1 Promoter Methylation in Endometrioid Endometrial Carcinoma","volume":"33","author":"Pasanen","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1158\/1078-0432.CCR-15-2878","article-title":"Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-Stage Endometrial Cancer\u2014Combined Analysis of the PORTEC Cohorts","volume":"22","author":"Stelloo","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1097\/PAS.0000000000001561","article-title":"DNA Mismatch Repair-Deficient Endometrial Carcinosarcomas Portend Distinct Clinical, Morphologic, and Molecular Features Compared With Traditional Carcinosarcomas","volume":"44","author":"Segura","year":"2020","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e17495","DOI":"10.1016\/j.heliyon.2023.e17495","article-title":"Clinicopathological Characteristics of Endometrial Carcinomas According to DNA Mismatch Repair Protein Status","volume":"9","author":"Aguiar","year":"2023","journal-title":"Heliyon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e13956","DOI":"10.1097\/MD.0000000000013956","article-title":"Microsatellite Instability and Manifestations of Angiogenesis in Stage IV of Sporadic Colorectal Carcinoma","volume":"98","author":"Otto","year":"2019","journal-title":"Medicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1007\/s12253-020-00811-5","article-title":"Diagnostic Accuracy of Immunohistochemistry for Mismatch Repair Proteins as Surrogate of Microsatellite Instability Molecular Testing in Endometrial Cancer","volume":"26","author":"Raffone","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/s41379-020-00680-y","article-title":"Interpretation of Mismatch Repair Protein Expression Using Obsolete Criteria Results in Discrepancies with Microsatellite Instability and Mutational Testing Results. Comment on Hechtman et al. Mod Pathol 2020; 33:871\u2013879","volume":"34","author":"Singh","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s12253-019-00784-0","article-title":"TCGA Molecular Subgroups in Endometrial Undifferentiated\/Dedifferentiated Carcinoma","volume":"26","author":"Travaglino","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1097\/PGP.0000000000000369","article-title":"Frequent Mismatch Repair Protein Deficiency in Mixed Endometrioid and Clear Cell Carcinoma of the Endometrium","volume":"36","author":"Leo","year":"2017","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/his.13976","article-title":"Clear Cell Endometrial Carcinoma and the TCGA Classification","volume":"76","author":"Travaglino","year":"2020","journal-title":"Histopathology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1007\/s12253-020-00829-9","article-title":"TCGA Classification of Endometrial Cancer: The Place of Carcinosarcoma","volume":"26","author":"Travaglino","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1097\/PAS.0000000000001461","article-title":"Endometrial Carcinomas with a \u201cSerous\u201d Component in Young Women Are Enriched for DNA Mismatch Repair Deficiency, Lynch Syndrome, and POLE Exonuclease Domain Mutations","volume":"44","author":"Conlon","year":"2020","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S64","DOI":"10.1097\/PGP.0000000000000518","article-title":"Endometrial Carcinoma Diagnosis: Use of FIGO Grading and Genomic Subcategories in Clinical Practice: Recommendations of the International Society of Gynecological Pathologists","volume":"38","author":"Soslow","year":"2019","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1097\/PGP.0000000000000491","article-title":"High-Grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations","volume":"38","author":"Murali","year":"2019","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/annonc\/mdw542","article-title":"Practical Guidance for Mismatch Repair-Deficiency Testing in Endometrial Cancer","volume":"28","author":"Stelloo","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.mpdhp.2020.03.002","article-title":"Interpretation of P16, P53 and Mismatch Repair Protein Immunohistochemistry in Gynaecological Neoplasia","volume":"26","author":"Palicelli","year":"2020","journal-title":"Diagn. Histopathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6877\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:21:28Z","timestamp":1785903688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":33,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156877"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156877","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]}}}