The ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) system identifies 4 molecular sub-types. Which sub-type carries the BEST prognosis with the highest 5-year survival?

• A MMR-deficient (MMRd) / microsatellite instability-high
• B p53-mutant (p53abn)
• C No specific molecular profile (NSMP), copy-number low
• D POLE-ultramutated (POLE-EDM) ✓

Explanation

POLE-ultramutated endometrial cancers, identified by somatic mutations in the exonuclease domain of POLE, carry an excellent prognosis (5-year DSS approaching 100%) despite often being high-grade tumours. This paradox is because POLE mutations generate abundant neoantigens that trigger strong immune surveillance. p53-mutant tumours have the worst prognosis (typically high-grade serous type). MMRd tumours have intermediate-good prognosis. NSMP is heterogeneous, with intermediate prognosis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.