The continuing evolution of endometrial carcinoma molecular classification: Risk stratification within the No Specific Molecular Profile (NSMP) subtype.

•NSMP molecular subtype includes ECs with diverse pathomolecular features and strikingly different clinical outcomes.•Two key features; ER status and grade discern ‘low-risk‘ and ‘high-risk NSMP’ enabling stratification of clinical care.•High grade (i.e. FIGO grade 3 endometrioid or non-endometrioid) and/or ER negativity can be identified on biopsy.•84% of NSMP EC are ‘low-risk’ (i.e. ER-positive AND low-grade) with excellent clinical outcomes, regardless of stage.•Together POLEmut and ‘low-risk NSMP’ EC encompass ∼50% of EC that could benefit from treatment de-escalation.