Endometrial carcinomas are categorized by the Cancer Genome Atlas (TCGA) into four molecular subtypes. A 45-year-old woman has grade 3 endometrial carcinoma with ultramutated phenotype (>100 mutations/Mb) and mutations in POLE (DNA polymerase epsilon). This TCGA molecular subtype has which prognosis?
- A Worst prognosis; corresponds to serous-like tumors
- B Best prognosis despite high grade histology; paradoxically excellent outcomes ✓
- C Intermediate prognosis; responds to progestins
- D Microsatellite stable with hypermethylation; intermediate prognosis
Explanation
The TCGA molecular classification of endometrial carcinomas (2013) identifies four subtypes: (1) POLE ultramutated — mutation in exonuclease domain of POLE causing proofreading deficiency, generating thousands of mutations, but paradoxically associated with EXCELLENT prognosis even when grade 3 or high-risk histology; (2) MSI-hypermutated (MLH1 hypermethylation) — intermediate prognosis; (3) Low copy number/microsatellite stable — often endometrioid, good prognosis; (4) High copy number/serous-like — TP53 mutated, worst prognosis. The POLE ultramutated paradox relates to immunogenicity and strong CD8+ T-cell infiltration.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.