American Association for Cancer Research
ccr-23-1397_supplementary_figure_s4_suppfs4.pdf (7.88 MB)

Supplementary Figure S4 from Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas

Download (7.88 MB)
journal contribution
posted on 2023-12-01, 08:45 authored by Amy Jamieson, Lisa Vermij, Claire J.H. Kramer, Jan J. Jobsen, Ina Jürgemlienk-Schulz, Ludy Lutgens, Jan Willem Mens, Marie A.D. Haverkort, Annerie Slot, Remi A. Nout, Jan Oosting, Joseph Carlson, Brooke E. Howitt, Philip P.C. Ip, Sigurd F. Lax, W. Glenn McCluggage, Naveena Singh, Jessica N. McAlpine, Carien L. Creutzberg, Nanda Horeweg, C. Blake Gilks, Tjalling Bosse

H&E, immunohistochemistry stains and relative copy number plot of a case diagnosed as low-grade EEC by ≥3 pathologists.


KWF Kankerbestrijding (DCS)



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. 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. 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. 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.

Usage metrics

    Clinical Cancer Research



    Ref. manager