The TCGA (The Cancer Genome Atlas) 2013 molecular classification of endometrial carcinoma identified four molecular subgroups. Which subgroup has the BEST prognosis despite being predominantly high-grade tumors?
- A POLE ultramutated — characterized by somatic mutations in the exonuclease domain of POLE gene, highest tumor mutational burden, best prognosis ✓
- B MSI-high (MMR deficient) — Lynch syndrome-associated, responds to immunotherapy, best overall prognosis
- C Copy-number low (microsatellite stable, p53 wild-type) — low mutation burden, excellent prognosis
- D Copy-number high (serous-like) — TP53 mutated, paradoxically better prognosis with platinum chemotherapy
Explanation
TCGA 2013 classified endometrial cancers into: (1) POLE ultramutated — best prognosis (5-year OS ~95% even for grade 3), despite high-grade morphology; (2) MSI-high/MMR-deficient — intermediate-good prognosis, responds to pembrolizumab; (3) copy-number low (no specific molecular feature, NSMP) — intermediate prognosis; (4) copy-number high/TP53 mutated (serous-like) — worst prognosis. POLE mutations occur in ~7-12% of endometrial cancers and confer hypersensitivity of tumor cells to immune surveillance (ultrahigh TMB triggers immune recognition). This classification (now incorporated into FIGO 2023 staging as molecular stage modifiers) guides adjuvant therapy decisions — POLE-mutated tumors may not need adjuvant radiotherapy.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.