Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Jamieson, A; Vermij, L; Kramer, CJH; Jobsen, JJ; Jürgemlienk-Schulz, I; Lutgens, L; Mens, JW; Haverkort, MAD; Slot, A; Nout, RA; Oosting, J; Carlson, J; Howitt, BE; Ip, PPC; Lax, SF; McCluggage, WG; Singh, N; McAlpine, JN; Creutzberg, CL; Horeweg, N; Gilks, CB; Bosse, T.
Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas.
Clin Cancer Res. 2023; 29(23):4949-4957
Doi: 10.1158/1078-0432.CCR-23-1397
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- Co-authors Med Uni Graz
- Lax Sigurd
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- Abstract:
- PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Female - administration & dosage
- Endometrial Neoplasms - pathology
- Carcinoma, Endometrioid - pathology
- Tumor Suppressor Protein p53 - genetics
- Retrospective Studies - administration & dosage
- Neoplasm Recurrence, Local - administration & dosage
- Canada - administration & dosage