Germline BRCA1/2 testing is recommended in women with ovarian cancer. Which histological subtype of epithelial ovarian carcinoma has the HIGHEST frequency of BRCA1/2 germline mutations?

• A Mucinous carcinoma
• B Clear cell carcinoma
• C High-grade serous carcinoma ✓
• D Endometrioid carcinoma

Explanation

High-grade serous carcinoma (HGSC) accounts for approximately 70–80% of all epithelial ovarian cancer deaths and has the strongest association with BRCA1/2 germline mutations; up to 15–20% of HGSC patients carry a germline BRCA1/2 mutation, and an additional 5–10% have somatic BRCA mutations. Mucinous carcinomas are rarely BRCA-associated and more often have KRAS mutations. Clear cell carcinoma (associated with endometriosis) has ARID1A and PIK3CA mutations. Endometrioid carcinoma shows lower rates of BRCA mutations. BRCA-mutant HGSC confers sensitivity to PARP inhibitors (olaparib maintenance therapy — SOLO-1 trial).

Reference: Shaw's Textbook of Gynaecology, 17th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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