Immunohistochemical Insights on Mismatch Repair Proteins in Ovarian Carcinoma: A North Indian Cohort Study
Payal Chawhan, Sonam Sharma, Mukul Singh
A
BSTRACT
Background:
Ovarian carcinoma (OC) is a leading cause of mortality among gynecological malignancies, with most cases diagnosed at advanced stages. High-grade serous carcinoma is the most common subtype, while endometrioid and clear cell carcinomas are more strongly associated with deficiencies in mismatch repair (MMR) proteins, particularly in Lynch syndrome. Detecting MMR deficiency (MMRd) by immunohistochemistry (IHC) serves as a cost-effective screening method with significant therapeutic implications, given its association with microsatellite instability and potential responsiveness to immune checkpoint inhibitors.
Objectives:
To evaluate MMR protein expression in OC using IHC and to correlate this expression with other clinicopathological parameters.
Materials and Methods:
A hospital-based, cross-sectional study was conducted over 24 months and included 50 histologically confirmed cases of OC. Formalin-fixed, paraffin-embedded tumor tissues were subjected to IHC staining for MutL protein homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and postmeiotic segregation increased 2 (PMS2). MMRd was defined as the loss of nuclear expression in tumor cells in the presence of positive internal controls.
Results:
All 50 cases demonstrated intact nuclear expression of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2). No case exhibited MMRd. The cohort encompassed various histological subtypes; however, MMR protein expression was preserved regardless of histological subtype or any other clinicopathological factors.
Conclusion:
This study found no MMRd in all the OC cases examined by IHC, suggesting a low prevalence of MMRd across high-grade serous and non-serous subtypes. However, given the limited sample size, larger multicenter studies in the Indian population are warranted to validate these findings and better define the clinical utility of routine MMR protein testing in OC management.