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• W4387157118 abstract "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 pathological and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort.Previously diagnosed stage I p53abn EC (POLE-wildtype, 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. Immunohistochemical profiling, next generation sequencing and shallow whole genome sequencing was performed. Kaplan-Meier's method was used for survival analysis.We identified 55 stage I p53abn low-grade EEC among 3387 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 immunohistochemical 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.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." @default.
• W4387157118 created "2023-09-30" @default.
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• W4387157118 date "2023-09-29" @default.
• W4387157118 modified "2023-10-01" @default.
• W4387157118 title "Clinical Behavior and Molecular Landscape of Stage I p53-abnormal Low-Grade Endometrioid Endometrial Carcinomas" @default.
• W4387157118 doi "https://doi.org/10.1158/1078-0432.ccr-23-1397" @default.
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• W4387157118 hasPublicationYear "2023" @default.
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