Which molecular subtype of endometrial carcinoma has the BEST prognosis and what is its key genetic feature?

• A Copy number high (serous-like); TP53 mutation
• B Mismatch repair deficient (MMRd); MLH1 promoter methylation or Lynch syndrome
• C Copy number low (endometrioid); CTNNB1 mutation
• D POLE (DNA polymerase epsilon)-ultramutated; POLE exonuclease domain mutations ✓

Explanation

The TCGA-based molecular classification of endometrial carcinoma includes four subtypes. POLE-ultramutated tumors have the best prognosis despite being histologically high-grade — they have an extremely high mutation burden due to proofreading domain mutations in POLE and are characterized by a high lymphocytic infiltration and excellent response to immune checkpoint inhibitors. Copy number high (TP53-mutated) tumors carry the worst prognosis. MMRd and NSMP (no specific molecular profile) have intermediate outcomes.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.