In the molecular classification of endometrial carcinoma, which subtype carries the BEST prognosis and is defined by pathogenic mutations in the exonuclease domain of POLE?

• A MSI-high (microsatellite instable)
• B POLE ultramutated ✓
• C NSMP (no specific molecular profile)
• D p53 aberrant (copy number high)

Explanation

The TCGA molecular classification of endometrial carcinoma identifies four groups: POLE ultramutated (best prognosis, >10% 5-year survival advantage), MSI-high (intermediate-good), NSMP (intermediate), and p53 aberrant/copy number high (worst prognosis). POLE ultramutated tumors harbor exonuclease domain mutations causing a hypermutation phenotype with abundant tumor-infiltrating lymphocytes and paradoxically excellent outcomes despite high histological grade. This classification is now incorporated into FIGO 2023 staging and guides adjuvant treatment decisions.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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