The TCGA (The Cancer Genome Atlas) molecular classification of endometrial cancer identifies four prognostic groups. Which molecular subgroup carries the BEST prognosis and is characterised by very high tumour mutational burden?

• A Microsatellite instability-high (MSI-H)
• B Copy number-low (endometrioid type)
• C Copy number-high (serous-like/p53 mutant)
• D POLE-ultramutated ✓

Explanation

POLE-ultramutated endometrial cancers carry pathogenic mutations in the exonuclease domain of the POLE gene, resulting in extremely high tumour mutational burden (TMB) and a favourable immune microenvironment. Despite often high-grade histology, POLE-ultramutated cancers have the best prognosis of all four TCGA groups. MSI-H carries intermediate-good prognosis; copy number-low has intermediate prognosis; copy number-high (p53-aberrant/serous-like) has the worst prognosis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.