The TCGA (The Cancer Genome Atlas) molecular classification of endometrial carcinoma identifies four prognostic subgroups. Which subgroup, characterised by POLE exonuclease domain mutations with an ultramutated phenotype, carries the most favourable prognosis despite high tumour grade?

• A Copy-number high (serous-like) — TP53 mutated
• B POLE-mutated (ultramutated) — best prognosis ✓
• C MSI-H (mismatch repair deficient) — MLH1 promoter hypermethylation
• D NSMP (No specific molecular profile) — copy-number low

Explanation

TCGA classifies endometrial carcinoma into four molecular groups: (1) POLE-mutated/ultramutated (~7%) — highest mutational burden, best prognosis despite high grade; (2) MSI-H/MMR-deficient (~28%) — mismatch repair deficiency, intermediate prognosis; (3) NSMP/copy-number low (~39%) — hormone receptor positive, intermediate prognosis; (4) Copy-number high/serous-like (~26%) — TP53 mutations, worst prognosis. POLE-mutated tumours may appear high-grade histologically but have excellent outcomes, potentially allowing deescalation of adjuvant therapy. This classification is now incorporated into WHO 2020 and ESGO/ESMO 2021 treatment guidelines.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.