The PORTEC-3 trial compared pelvic radiotherapy alone versus chemoradiation in high-risk endometrial cancer. Which molecular subtype of endometrial cancer identified by TCGA (The Cancer Genome Atlas) classification has the BEST prognosis and does NOT benefit from adjuvant chemotherapy?
- A POLE ultramutated (POLEmut) subtype — extremely high mutation load with paradoxically excellent prognosis ✓
- B MMR-deficient (MSI-H) subtype — mismatch repair deficiency with moderate mutation load
- C Copy number high (serous-like) subtype — TP53-mutated with aggressive behavior
- D Copy number low/no specific molecular profile (NSMP) subtype — includes endometrioid Grade 1-2
Explanation
TCGA (2013) and subsequent studies established four molecular subtypes of endometrial cancer: (1) POLE ultramutated — highest tumor mutation burden (TMB) due to POLE exonuclease domain mutations, paradoxically the BEST prognosis regardless of histological grade; (2) MMR-deficient (MSI-H) — intermediate prognosis, benefits from immunotherapy (pembrolizumab); (3) Copy number low/NSMP — intermediate; (4) Copy number high/TP53-mutated — worst prognosis, resembles serous carcinoma. POLEmut tumors have high immune infiltration and near-universal cure with surgery alone in early-stage disease. The PORTEC-4a trial is evaluating whether POLEmut patients can safely omit radiotherapy.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.