The TCGA (The Cancer Genome Atlas) 2013 molecular classification of endometrial carcinoma identified 4 prognostic groups. The ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) algorithm classifies endometrial cancer into these groups using practical immunohistochemistry and molecular markers. Which of the following correctly matches the molecular subtype with its key defining feature and prognosis?

• A POLE ultramutated — worst prognosis; associated with Lynch syndrome
• B Mismatch repair deficient (MMRd) — Lynch syndrome associated; intermediate prognosis; PD-L1/immunotherapy responsive ✓
• C Copy number high (CNH)/serous-like — TP53 wildtype; best prognosis
• D NSMP (no specific molecular profile) — highest mutation burden; intermediate-to-favourable prognosis

Explanation

The four TCGA/ProMisE molecular subtypes of endometrial cancer: (1) POLE ultramutated — POLE exonuclease domain mutation, highest tumour mutational burden, paradoxically the BEST prognosis despite appearing high-grade; (2) MMR deficient — microsatellite instability-high (MSI-H), associated with Lynch syndrome (hereditary endometrial cancer), intermediate-to-poor prognosis, excellent response to PD-1/PD-L1 immunotherapy (pembrolizumab); (3) p53-mutated/Copy number high — TP53 mutation, resembles serous carcinoma, WORST prognosis; (4) NSMP (No Specific Molecular Profile) — intermediate prognosis. Option B is correct as MMRd is Lynch-associated with immunotherapy responsiveness.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.