{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:00:20Z","timestamp":1770814820404,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy Cluj-Napoca, Romania, Doctoral Research Program","award":["PCD 771\/8\/11.01.2023"],"award-info":[{"award-number":["PCD 771\/8\/11.01.2023"]}]},{"name":"European Union\u2014NextGenerationEU and Romanian Government under National Recovery and Resilience Plan for Romania","award":["760072\/23.05.2023"],"award-info":[{"award-number":["760072\/23.05.2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive, heterogeneous, and lethal malignancies in humans. Mismatch repair (MMR) proteins constitute a fundamental component of the DNA mismatch repair pathway, which is responsible for correcting replication-associated errors, including incorrect base pairings and small insertions or deletions. This study aims to evaluate the immunohistochemical expression of MSH2, MSH6, MLH1, and PMS2 in resected PDAC and to analyze their association with pTNM stage, perineural and lymphovascular invasion, HER2 and HER3 expression, and tumor volume. Methods: A cohort of 106 patients with currative intent Whipple procedure was evaluated, their corresponding paraffin blocks and slides were analyzed using tissue microarray. Immunohistochemical analysis of MLH1, PMS2, MSH2, and MSH6 was performed. Patients were grouped based on MMR expression profiles: isolated MutS loss (MSH2\/MSH6), and isolated MutL loss (MLH1\/PMS2). Results: Among the 106 subjects evaluated, 13 (12.3%) exhibited isolated MutS complex loss and 16 (15.1%) showed MutL complex loss. A total of 7 patients (6.6%) demonstrated concurrent loss of all four MMR proteins, representing a pattern suggestive of MMR deficiency MSI-H. These ones were significantly younger (median 56 vs. 64 years, p = 0.0492) and had distinct T-stage distribution (p = 0.0237). Two intermediate subgroups were identified: five patients with isolated MutL loss and one patient with isolated MutS loss. HER3 positivity was observed in 3\/5 of the intermediate MutL cases and HER2 positivity in only one. Conclusions: MMR deficiency and potential MSI-H status were identified to be relevant prognostic biomarkers for pancreatic cancer patients, with MSI-H patients displaying a younger age and distinct tumor features.<\/jats:p>","DOI":"10.3390\/jcm15041411","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T09:15:12Z","timestamp":1770801312000},"page":"1411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mismatch Repair Protein and Microsatellite Instability Analysis in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1239-4337","authenticated-orcid":false,"given":"Ioan C\u0103t\u0103lin","family":"Bodea","sequence":"first","affiliation":[{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"\u201dOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-6428","authenticated-orcid":false,"given":"Andra","family":"Ciocan","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"\u201dOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9618-9359","authenticated-orcid":false,"given":"Florin Vasile","family":"Zaharie","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"\u201dOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7968-908X","authenticated-orcid":false,"given":"Radu","family":"Vidra","sequence":"additional","affiliation":[{"name":"\u201dOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"MEDFUTURE Biomedical Research Institute, Department of Personalized Medicine and Rare Diseases, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0218tefan","family":"Ursu","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u0103zvan Alexandru","family":"Ciocan","sequence":"additional","affiliation":[{"name":"Department of Surgery-Practical Abilities, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Marinescu Street, No. 23, 400337 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9963-561X","authenticated-orcid":false,"given":"R\u0103zvan George","family":"Bogdan","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2342-4311","authenticated-orcid":false,"given":"Sorana D.","family":"Bolboac\u0103","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy Cluj-Napoca, Louis Pasteur Street, No. 6, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6620-1494","authenticated-orcid":false,"given":"Filip Cristian","family":"Tocoian","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"\u201dOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bobe","family":"Petrushev","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Street No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana Liana","family":"Popa","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Street No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadim","family":"Al Hajjar","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"\u201dOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3389\/fonc.2024.1521788","article-title":"Global, regional, and national burden of pancreatic cancer and its attributable risk factors from 2019 to 2021, with projection to 2044","volume":"14","author":"Li","year":"2025","journal-title":"Front. 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