Which molecular subtype of endometrial carcinoma defined by TCGA (The Cancer Genome Atlas) classification carries the BEST prognosis, characterised by markedly elevated somatic mutation burden?

• A POLE-ultramutated subtype ✓
• B Microsatellite instability-high (MSI-H) hypermutated subtype
• C Copy-number-high (serous-like) subtype
• D Copy-number-low (endometrioid) subtype

Explanation

The POLE-ultramutated subtype (somatic mutations in the exonuclease domain of POLE gene) carries the best prognosis despite often high-grade histology, due to a highly immunogenic tumour microenvironment and robust anti-tumour immune response. MSI-H is hypermutated with intermediate prognosis and is predictive of immunotherapy (pembrolizumab) response. The copy-number-high (serous-like) subtype has the worst prognosis. POLE testing is now incorporated into standard management to de-escalate adjuvant treatment.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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