Clinicopathological Correlation of BRCA1 Status in High-Grade Serous Ovarian Carcinoma via IHC and NGS

Abstract

BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is the most aggressive subtype of epithelial ovarian cancer and is frequently associated with BRCA1 dysfunction. This study aimed to evaluate the clinicopathological correlation of BRCA1 expression and mutation status assessed by immunohistochemistry (IHC) and next-generation sequencing (NGS) with the Whole Exome Sequencing (WES) approach. METHODS: A retrospective observational study was conducted on thirty-six formalin-fixed paraffin-embedded HGSOC samples. BRCA1 expression was evaluated by IHC using a 10% nuclear staining cutoff. BRCA1 mutation profiling was performed using NGS with a whole-exome sequencing (WES) approach. Clinicopathological variables were analyzed using Fisher's exact test. RESULT: Abnormal BRCA1 expression was observed in 11.1% of cases, while BRCA1 mutations were detected in 27.8%. Most mutations were somatic (70%) and predominantly loss-of-function variants (90%). A significant association was found between abnormal BRCA1 expression and younger age (p = 0.023), whereas no association was observed with other clinicopathological parameters. CONCLUSION: BRCA1 expression loss in HGSOC is associated with younger patient age. The discordance between IHC and mutation status highlights the complementary role of protein expression and molecular testing. A combined IHC-NGS approach may improve the identification of BRCA1 deficiency and support therapeutic decision-making, particularly in the context of targeted therapy.

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