The ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) molecular classification divides endometrial carcinoma into 4 subgroups. Which subgroup has the BEST prognosis and is associated with POLE (proofreading exonuclease domain) mutations?
- A MSI-H (mismatch repair deficient) — intermediate/favorable prognosis, responds to immunotherapy
- B p53 mutant (TP53 mutation) — best prognosis, usually low-grade endometrioid
- C NSMP (no specific molecular profile) — best prognosis, usually estrogen receptor-positive
- D POLE ultramutated — excellent prognosis (>90% 5-year DSS), high tumor mutational burden ✓
Explanation
The TCGA-derived molecular classification (mirrored in ProMisE) includes four groups: (1) POLE ultramutated — best prognosis (>90% 5-year disease-specific survival) due to extreme tumor mutational burden generating immunogenic neoantigens; (2) MMRd (MSI-H) — intermediate-favorable; (3) NSMP (copy number low) — intermediate; (4) p53 aberrant (copy number high) — worst prognosis, predominantly high-grade serous-like histology. POLE mutations paradoxically carry excellent prognosis despite high grade, guiding adjuvant treatment de-escalation. Immunotherapy (pembrolizumab) is most effective in MMRd.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.