Endometrial carcinoma is now classified by The Cancer Genome Atlas (TCGA) into four molecular subgroups. Which molecular subgroup has the BEST prognosis despite often showing high-grade morphology?
- A MSI-high (microsatellite instability-high) hypermutated group
- B POLE (polymerase epsilon) ultramutated group ✓
- C Copy number-low (CN-low), TP53 wildtype group
- D Copy number-high (CN-high), TP53 mutated group (serous-like)
Explanation
The TCGA/ProMisE molecular classification of endometrial carcinoma identifies four prognostic groups: (1) POLE ultramutated (POLE exonuclease domain mutations, extremely high mutation burden >100 mut/Mb) — paradoxically best prognosis despite grade 3 morphology, due to high neoantigen load generating strong anti-tumor immunity; (2) MSI-H hypermutated (MLH1 promoter methylation or Lynch syndrome MMR deficiency) — intermediate-good prognosis, benefits from pembrolizumab; (3) CN-low/no specific molecular profile — intermediate prognosis, largely endometrioid; (4) CN-high/TP53 mutant (serous-like) — worst prognosis (equivalent to papillary serous carcinoma). Importantly, a POLE-ultramutated tumor classified as grade 3 endometrioid still has excellent prognosis and may not need adjuvant radiotherapy.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.