The 2020 WHO/ESGO molecular classification of endometrial carcinoma divides tumors into four prognostic groups. A 55-year-old woman has endometrioid grade 1 endometrial cancer with POLE exonuclease domain mutation on next-generation sequencing. Which statement BEST describes the prognostic significance and clinical implication?
- A POLE-mutant tumors have worst prognosis and require extended adjuvant chemotherapy
- B POLE-mutant tumors are ultramutated with excellent prognosis, potentially enabling de-escalation of adjuvant treatment ✓
- C POLE-mutant endometrial cancers respond poorly to immunotherapy unlike MSI-H tumors
- D POLE mutation predicts benefit from anti-VEGF therapy regardless of stage
Explanation
The TCGA/ProMisE/ESGO 2020 molecular classification divides endometrial cancer into: (1) POLE-ultramutated — excellent prognosis even at high grade; (2) MSI-high (dMMR) — intermediate-good prognosis, highly immunogenic; (3) NSMP (no specific molecular profile, copy number low) — intermediate prognosis; (4) p53-mutant (NSMP with TP53 mutation/copy number high) — worst prognosis. POLE-ultramutated tumors paradoxically have the best prognosis despite high-grade histology, supporting de-escalation of adjuvant radiotherapy. They also respond extremely well to immune checkpoint inhibitors (very high tumor mutational burden). The ESGO 2021 guidelines incorporate molecular classification into risk stratification and adjuvant treatment decisions.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.