A 55-year-old woman undergoes surgery for an ovarian mass with a final histology showing a low-grade serous carcinoma (LGSC). Compared to high-grade serous carcinoma (HGSC), which molecular pathway is characteristically altered in LGSC?

• A KRAS/BRAF mutations with relatively intact TP53 ✓
• B TP53 mutation with homologous recombination deficiency
• C BRCA1/2 germline mutations with PARP inhibitor sensitivity
• D MSI-high phenotype with Lynch syndrome association

Explanation

Low-grade serous carcinoma (LGSC) arises via the Type I pathway from serous borderline tumours and is characterized by KRAS, BRAF, or NRAS mutations with typically wild-type TP53. In contrast, HGSC (Type II pathway) has near-universal TP53 mutation with frequent BRCA1/2 alterations and homologous recombination deficiency. This molecular distinction explains LGSC's relative chemoresistance and the rationale for MEK inhibitor (e.g., binimetinib) trials in LGSC. Lynch syndrome/MSI-high is more characteristic of endometrioid and clear-cell ovarian carcinomas.

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

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Written and medically reviewed by the StethoPrep medical team.