Which molecular subtype of endometrial cancer according to the TCGA/ProMisE classification has the BEST prognosis regardless of histological grade or stage?

• A Mismatch repair-deficient (MMRd)
• B POLE-ultramutated (POLEmut) ✓
• C p53-mutant (p53mut)
• D Non-specific molecular profile (NSMP)

Explanation

POLE-ultramutated endometrial cancers harbour somatic pathogenic mutations in the exonuclease domain of DNA polymerase epsilon (POLE), resulting in an ultramutated phenotype. Despite often being high-grade (Grade 3) or serous-like histologically, POLEmut tumours have an exceptionally favourable prognosis — 5-year cancer-specific survival approaches 100%. This subtype is also characterised by high tumour mutational burden and potential immunotherapy sensitivity. The p53-mutant subtype has the worst prognosis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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