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The study investigates the expression of mismatch repair proteins in pancreatic ductal adenocarcinoma and their prognostic significance.

February 12, 2026Journal of Clinical Medicine0 citationsOpen Access

Mismatch Repair Protein and Microsatellite Instability Analysis in Pancreatic Ductal Adenocarcinoma

IBIoan Cătălin BodeaIuliu Hațieganu University of Medicine and Pharmacy ACAndra CIOCAN FZFlorin Vasile ZaharieIuliu Hațieganu University of Medicine and Pharmacy

Key Points

The study investigates the expression of mismatch repair proteins in pancreatic ductal adenocarcinoma and their prognostic significance.
Analyzed 106 resected pancreatic cancer samples using immunohistochemical methods.
Grouped patients based on MMR protein expression profiles: isolated MutS loss and isolated MutL loss.
Evaluated associations of MMR expression with clinical features like pTNM stage and tumor volume.
12.3% of patients exhibited isolated MutS complex loss; 15.1% showed MutL complex loss.
6.6% demonstrated concurrent loss of all four MMR proteins, indicative of MMR deficiency MSI-H.
Younger age and distinct T-stage distribution were observed in MSI-H patients.

Abstract

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.

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