The TCGA molecular classification of endometrial carcinoma identifies four subgroups. Which molecular subgroup carries the BEST prognosis and is characterised by ultra-high somatic mutation burden?

• A Microsatellite instability-high (MSI-H, hypermutated)
• B Copy number low (CN-low, endometrioid)
• C Copy number high (CN-high, serous-like)
• D POLE ultramutated (POLE-EDM) ✓

Explanation

The TCGA (Cancer Genome Atlas) 2013 molecular classification of endometrial carcinoma: (1) POLE ultramutated — hotspot mutations in exonuclease domain of DNA polymerase epsilon → extremely high tumour mutation burden → best prognosis (5-year DSS ~95%); (2) MSI-H hypermutated — MLH1 promoter hypermethylation or Lynch syndrome MMR gene mutations → good prognosis; (3) CN-low — CTNNB1 mutations, typically endometrioid Grade 1–2 → intermediate prognosis; (4) CN-high / serous-like — TP53 mutations, CCNE1 amplification → worst prognosis. POLE status guides adjuvant therapy decisions in current ProMisE/TransPORTEC classifications used clinically.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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