According to the ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) molecular classification adopted in WHO 2020 and FIGO 2023, which molecular subtype of endometrial carcinoma carries the worst prognosis?
- A POLE-ultramutated (POLE mutant)
- B Mismatch repair-deficient (MMRd) / microsatellite instability-high (MSI-H)
- C No specific molecular profile (NSMP) / p53 wild-type
- D p53-aberrant (TP53 mutant) ✓
Explanation
The four molecular subtypes of endometrial carcinoma (TCGA/ProMisE) have the following prognosis (best to worst): (1) POLE ultramutated — best prognosis despite high grade, > 95% 5-year PFS; (2) MMRd/MSI-H — intermediate prognosis, also a predictive biomarker for pembrolizumab response; (3) NSMP/p53 wild-type — intermediate; (4) p53-aberrant (TP53 mutant) — worst prognosis, most commonly associated with serous-type or high-grade endometrioid carcinoma, frequent TP53 mutations, and copy number-high genomic instability (similar to HGSC ovarian). p53-aberrant tumours have 5-year survival < 50% and are often treated with carboplatin-paclitaxel chemotherapy.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.