The ProMisE molecular classification system for endometrial carcinoma (based on TCGA) identifies four molecular subgroups. Which subgroup has the BEST prognosis?
- A Microsatellite instability-high (MSI-H)
- B POLE ultramutated (POLEmut) ✓
- C No specific molecular profile (NSMP)
- D p53 abnormal (p53abn)
Explanation
The TCGA/ProMisE molecular classification (4 groups): (1) POLE ultramutated — pathogenic POLE exonuclease domain mutations; best prognosis with ~100% 5-year DSS in early stage; (2) MSI-H/MMRd — intermediate prognosis, Lynch syndrome association; (3) NSMP (copy number low) — intermediate prognosis; (4) p53 abnormal (copy number high) — worst prognosis, serous-like behaviour. POLEmut endometrial cancers paradoxically have massive tumour mutational burden but excellent outcomes, possibly due to immune checkpoint activation by neoantigens. This molecular classification now informs ESGO/ESTRO/ESP 2020 guidelines for adjuvant therapy decisions (POLEmut = de-escalate adjuvant treatment even in stage III).
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.