Immunohistochemical Evaluation of Mismatch Repair Deficiency in Prostate Cancer

Abstract

Introduction: Prostate cancer is a leading malignancy among men worldwide, with rising incidence in South Asia. Traditional prognostic parameters such as Gleason score and PSA are being complemented by molecular biomarkers, including mismatch repair (MMR) deficiency, which has gained importance due to its association with microsatellite instability and therapeutic responsiveness. This study aimed to evaluate the frequency and patterns of MMR protein loss in prostate carcinoma using immunohistochemistry (IHC).

Methodology: This cross-sectional study was conducted at the Armed Forces Institute of Pathology (AFIP), Rawalpindi, between June 2023 and July 2024. Seventy-two histologically confirmed cases of prostate carcinoma were analyzed. Formalin-fixed, paraffin-embedded tissue blocks underwent IHC staining for MLH1, MSH2, MSH6, and PMS2. Nuclear staining loss in tumor cells, with intact internal controls, was interpreted as MMR deficiency. Data were statistically analyzed using SPSS version 26.0, with p < 0.05 considered significant.

Results: The mean patient age was 71.4 ± 8.2 years. Acinar adenocarcinoma was the predominant histological subtype (81.9%). MMR deficiency was identified in 16 cases (22.2%), with isolated losses observed for PMS-2 (13.9%) and MSH-6 (16.7%) being most frequent. No significant associations were found between MMR deficiency and clinicopathological parameters such as age, histological subtype, or tumor stage.

Conclusion: A substantial proportion of prostate carcinoma cases demonstrated MMR protein loss, predominantly involving PMS-2 and MSH-6. Routine IHC evaluation for MMR proteins may provide clinically relevant insights, supporting personalized treatment strategies and genetic counseling in prostate cancer.