{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jamieson A"],"funding":["KWF Kankerbestrijding (DCS)","KWF Kankerbestrijding"],"pagination":["4949-4957"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10690141"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(23)"],"pubmed_abstract":["<h4>Purpose</h4>The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort.<h4>Experimental design</h4>Previously diagnosed stage I p53abn EC (POLE-wild-type, mismatch repair-proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included. Pathology review was performed by six expert gynecologic pathologists blinded to p53 status. IHC profiling, next-generation sequencing, and shallow whole-genome sequencing was performed. Kaplan-Meier method was used for survival analysis.<h4>Results</h4>We identified 55 stage I p53abn low-grade EEC among 3,387 cases (2.5%). On pathology review, 17 cases (31%) were not diagnosed as low-grade EEC by any pathologists, whereas 26 cases (47%) were diagnosed as low-grade EEC by at least three pathologists. The IHC and molecular profile of the latter cases were consistent with low-grade EEC morphology (ER/PR positivity, patchy p16 expression, PIK3CA and PTEN mutations) but they also showed features of p53abn EC (TP53 mutations, many copy-number alterations). These cases had a clinically relevant risk of disease recurrence (5-year recurrence-free survival 77%), with pelvic and/or distant recurrences observed in 12% of the patients.<h4>Conclusions</h4>A subset of p53abn EC is morphologically low-grade EEC and exhibit genomic instability. Even for stage I disease, p53abn low-grade EEC are at substantial risk of disease recurrence. These findings highlight the clinical relevance of universal p53-testing, even in low-grade EEC, to identify women at increased risk of recurrence."],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pubmed_title":["Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas."],"pmcid":["PMC10690141"],"funding_grant_id":["CKVO 90-01","CTKO 1990-01","11629","12995"],"pubmed_authors":["Howitt BE","Ip PPC","McAlpine JN","Vermij L","Bosse T","Kramer CJH","Gilks CB","Lutgens L","Mens JW","Jobsen JJ","Lax SF","Horeweg N","Oosting J","Carlson J","Haverkort MAD","McCluggage WG","Slot A","Singh N","Jamieson A","Creutzberg CL","Nout RA","Jurgemlienk-Schulz I"],"additional_accession":[]},"is_claimable":false,"name":"Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas.","description":"<h4>Purpose</h4>The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort.<h4>Experimental design</h4>Previously diagnosed stage I p53abn EC (POLE-wild-type, mismatch repair-proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included. Pathology review was performed by six expert gynecologic pathologists blinded to p53 status. IHC profiling, next-generation sequencing, and shallow whole-genome sequencing was performed. Kaplan-Meier method was used for survival analysis.<h4>Results</h4>We identified 55 stage I p53abn low-grade EEC among 3,387 cases (2.5%). On pathology review, 17 cases (31%) were not diagnosed as low-grade EEC by any pathologists, whereas 26 cases (47%) were diagnosed as low-grade EEC by at least three pathologists. The IHC and molecular profile of the latter cases were consistent with low-grade EEC morphology (ER/PR positivity, patchy p16 expression, PIK3CA and PTEN mutations) but they also showed features of p53abn EC (TP53 mutations, many copy-number alterations). These cases had a clinically relevant risk of disease recurrence (5-year recurrence-free survival 77%), with pelvic and/or distant recurrences observed in 12% of the patients.<h4>Conclusions</h4>A subset of p53abn EC is morphologically low-grade EEC and exhibit genomic instability. Even for stage I disease, p53abn low-grade EEC are at substantial risk of disease recurrence. These findings highlight the clinical relevance of universal p53-testing, even in low-grade EEC, to identify women at increased risk of recurrence.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2026-05-29T00:47:18.967Z","creation":"2025-04-05T11:46:05.557Z"},"accession":"S-EPMC10690141","cross_references":{"pubmed":["37773079"],"doi":["10.1158/1078-0432.CCR-23-1397"]}}