Evaluation of Mismatch Repair (MMR) and Breast Cancer-1 (BRCA-1) Statuses in Epithelial Ovarian Cancer - Research Article

Sep 23, 2026

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Study assesses BRCA1 and mismatch repair (MMR) protein expression in epithelial ovarian cancers using immunohistochemistry (IHC) and evaluates clinicopathological correlations. IHC was performed for BRCA1, MLH1, MSH2, MSH6, and PMS2 and compared with clinical and pathological variables. From 508 ovarian tissue specimens, 24.01% showed invasive epithelial ovarian cancer; 49 cases had sufficient tumor for detailed analysis. Deficient MMR occurred in 51% and total BRCA1 loss in 36.7%, with dMMR not linked to grade or high-grade features.

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Abstract

Introduction

Materials and Methods

RESEARCH ARTICLE | Editorial Proc | ess: Submission:05/04/2025 Acceptance:12/07/2025 Published:12/26/2025 | | --- | --- | Evaluation of Mismatch Repair (MMR) and Breast Cancer-1 (BRCA-1) Statuses in Epithelial Ovarian Cancer Richa Singh1, Preeti Agarwal1*, Shuchi Agrawal2, Eva Raman2, Vandana Solanki2, Puneet Prakash3, Malti Kumari Maurya1, Riddhi Jaiswal1, Sameer Gupta3 Abstract Introduction: This study aims to evaluate the expression of BRCA1 and MMR proteins using immunohistochemistry (IHC) in epithelial ovarian cancers and to explore their clinicopathological correlations. Methodology: IHC was performed and interpreted for BRCA1, MLH1, MSH2, MSH6, and PMS2 . The results were then compared with clinical and pathological variables. Results: Over a period of 19 months, 508 specimens containing ovarian tissue were received, either as part of a hysterectomy or as isolated samples for various indications. Among these, 24.01%(122/508) showed invasive epithelial ovarian cancer. Of these, 49 resection specimens had sufficient tumor tissue for detailed immunohistochemistry (IHC) analysis and were included in the study. Among the evaluated cases, 51%(25/49) of invasive epithelial ovarian cancers exhibited deficient mismatch repair (dMMR) . No significant correlation was observed between dMMR and pMMR with respect to grade, cellularity, and high-grade features. Patients with dMMR showed better survival, which may be due to improved response to chemotherapy in these cases. Total loss of BRCA1 was seen in 36.7%(18/49) of cases. BRCA1 loss was associated with poor predictive factors but had better prognosis. Loss of BRCA1 was associated with aggressive tumors but had better response to chemotherapy. Both MMRand BRCA1 were independent variables. The overall survival of our patient population with epithelial ovarian cancer was 86.8% . Conclusion: A significant number of patients displayed dMMR and BRCA1 loss by IHC. These patients may benefit from targeted therapy, and IHC may serve as an acceptable technique for each evaluation. Keywords: Epithelial cancers of ovary-BRCA1-MMR-Immunohistochemistry-ovarian cancers Asian Pac J Cancer Prev, 26 (12), 4447-4456 Introduction India presents with appreciable geographic variation in the incidence of ovarian cancer, about 50% of cases occur in the age group of 45-65 years [1]. It contributes to around 5.9% of total cancer cases in the country with a mean age-adjusted rate of 5.6 per 100000 populations [2] . The tumors ofthe ovary are classified into-epithelial-stromal tumors, sex cord-stromal tumors, and germ-cell tumors based on the anatomic structure from which the tumor originates. Epithelial cancers in the ovary are the most common and are broadly divided into serous, mucinous, endometroid, clear cell, and brenner subtypes based on histomorphological features. The five-year relative survival rate is approximately 30-50% cumulative of all stages [3] . As ovarian cancer does not present with specific symptoms at the disease onset, the symptoms present when the disease spreads to the abdominal cavity and peritoneum, the screening tests like transvaginal sonography and serum cancer antigen-125 (CA-125) have limited role in early detection of the cancer. The standard treatment regimen includes a combination of surgery and platinum or taxane-based adjuvant chemotherapy, which may show relapse and may result in early mortality. Conventional chemotherapy is the main treatment for ovarian cancer. Although BRCA1(Breast Cancer gene 1) is a known target for treatment, it needs special molecular tests, so it is not commonly used in managing ovarian epithelial cancer [3]. A family history of ovarian, breast, or endometrial cancer can increase the risk of inheriting autosomal dominant genes. The cumulative risk of ovarian cancer is 49% in those with BRCA1 mutations and 21% in those with BRCA2 (Breast Cancer gene 2) mutations [4] . BRCA1 mutations can be both inherited or acquired due to

FAQs

What proteins were evaluated in the study, and how were they measured?

The study evaluated BRCA1 and MMR proteins MLH1, MSH2, MSH6, and PMS2. Protein expression was measured using immunohistochemistry (IHC) and interpreted for clinicopathological correlations.

What proportion of cases showed deficient mismatch repair (dMMR) and BRCA1 loss?

Among evaluated invasive epithelial ovarian cancers, 51% showed deficient mismatch repair (dMMR). Total loss of BRCA1 was observed in 36.7% of cases.

Did dMMR correlate with tumor grade or high-grade features?

No significant correlation was observed between dMMR and pMMR regarding grade, cellularity, and high-grade features.

Sep 23, 2026

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