biostudies-literatureUnknown15(1)Darbandsari ATerry Fox Research InstituteCanadian Institute of Health Research OVCARE Carraresi VGH UBC Hospital FoundationMichael Smith Foundation for Health ResearchEndometrial cancer (EC) has four molecular subtypes with strong prognostic value and therapeutic implications. The most common subtype (NSMP; No Specific Molecular Profile) is assigned after exclusion of the defining features of the other three molecular subtypes and includes patients with heterogeneous clinical outcomes. In this study, we employ artificial intelligence (AI)-powered histopathology image analysis to differentiate between p53abn and NSMP EC subtypes and consequently identify a sub-group of NSMP EC patients that has markedly inferior progression-free and disease-specific survival (termed 'p53abn-like NSMP'), in a discovery cohort of 368 patients and two independent validation cohorts of 290 and 614 from other centers. Shallow whole genome sequencing reveals a higher burden ofNature communications4973https://www.ebi.ac.uk/biostudies/studies/S-EPMC11208496biostudies-literatureAI-based histopathology image analysis reveals a distinct subset of endometrial cancers.PMC11208496Huntsman DGFarahani HMcAlpine JNDouglas MWiens MGilks CBDarbandsari AAhmadvand PCochrane DTalhouk AKommoss SBashashati AFarnell DAbolmaesumi PSingh NJamieson AJones SJMAsadi MKhajegili Mirabadi ALeung SfalseAI-based histopathology image analysis reveals a distinct subset of endometrial cancers.Endometrial cancer (EC) has four molecular subtypes with strong prognostic value and therapeutic implications. The most common subtype (NSMP; No Specific Molecular Profile) is assigned after exclusion of the defining features of the other three molecular subtypes and includes patients with heterogeneous clinical outcomes. In this study, we employ artificial intelligence (AI)-powered histopathology image analysis to differentiate between p53abn and NSMP EC subtypes and consequently identify a sub-group of NSMP EC patients that has markedly inferior progression-free and disease-specific survival (termed 'p53abn-like NSMP'), in a discovery cohort of 368 patients and two independent validation cohorts of 290 and 614 from other centers. Shallow whole genome sequencing reveals a higher burden of2024-01-01T00:00:00Z2024 Jun2025-04-04T21:22:10.535Z2025-04-04T21:22:10.535ZS-EPMC112084963892635710.1038/s41467-024-49017-2