The ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) molecular classification introduced by TCGA uses 4 subtypes. Which molecular subtype carries the BEST prognosis despite being classified as high histological grade?

• A POLE ultramutated subtype ✓
• B Mismatch repair deficient (MMRd) subtype
• C p53 mutant (aberrant) subtype
• D No specific molecular abnormality (NSMP) subtype

Explanation

The TCGA/ProMisE molecular classification identifies 4 endometrial cancer subtypes: (1) POLE ultramutated — highest tumour mutational burden, excellent prognosis (>95% 5-year OS) even with high-grade histology; (2) MMRd (microsatellite instable) — intermediate prognosis, associated with Lynch syndrome; (3) NSMP (no specific molecular profile) — intermediate prognosis; (4) p53 mutant — worst prognosis, associated with uterine serous carcinoma. POLE ultramutated tumours paradoxically carry the best prognosis despite being histologically high grade, leading to discussion about de-escalating adjuvant therapy in this group.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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