Molecular classification of endometrial carcinoma per ProMisE/TCGA identifies four groups. Which molecular subgroup has the BEST prognosis?

• A Mismatch repair deficient (MMRd)
• B Copy number high (TP53 abnormal)
• C Copy number low (NSMP — no specific molecular profile)
• D POLE (polymerase epsilon) ultramutated ✓

Explanation

POLE-ultramutated endometrial carcinomas have the best prognosis despite high histological grade, because the ultrahigh mutation burden generates neoantigens that drive robust immune surveillance. These tumours rarely recur and have excellent 5-year survival even at advanced stages. TP53-abnormal (copy number high, serous-like) has the worst prognosis. MMRd has intermediate prognosis and high response to immune checkpoint inhibitors. NSMP is the most common group with intermediate prognosis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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