A 40-year-old woman has bilateral ovarian masses, ascites, and elevated CA-125 of 2800 U/mL. Staging laparotomy reveals high-grade serous ovarian cancer FIGO stage IIIC with >1 cm residual disease after surgery. Which molecular alteration is most commonly found in high-grade serous ovarian carcinoma (HGSOC)?
- A K-RAS mutation at codon 12
- B KRAS or BRAF mutation leading to MAPK pathway activation
- C PTEN loss leading to PI3K/AKT pathway activation
- D TP53 mutation (present in >96% of HGSOC) ✓
Explanation
High-grade serous ovarian carcinoma (HGSOC) is the most common and most lethal subtype of ovarian cancer. Its defining molecular hallmark is TP53 mutation, present in >96% of cases. Unlike the 'low-grade pathway' (which involves KRAS/BRAF mutations), HGSOC follows the 'high-grade pathway' characterized by near-universal TP53 mutation, chromosomal instability, BRCA1/2 mutations (~20% germline, ~6% somatic), and copy number variations. KRAS mutations are the hallmark of low-grade serous carcinoma and mucinous carcinoma. PTEN loss is characteristic of endometrioid ovarian carcinoma. Understanding these molecular pathways has led to targeted therapies including PARP inhibitors in BRCA-mutated cases.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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Written and medically reviewed by the StethoPrep medical team.