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Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas.
Jamieson, Amy; Vermij, Lisa; Kramer, Claire J H; Jobsen, Jan J; Jürgemlienk-Schulz, Ina; Lutgens, Ludy; Mens, Jan Willem; Haverkort, Marie A D; Slot, Annerie; Nout, Remi A; Oosting, Jan; Carlson, Joseph; Howitt, Brooke E; Ip, Philip P C; Lax, Sigurd F; McCluggage, W Glenn; Singh, Naveena; McAlpine, Jessica N; Creutzberg, Carien L; Horeweg, Nanda; Gilks, C Blake; Bosse, Tjalling.
Afiliação
  • Jamieson A; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, Canada.
  • Vermij L; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
  • Kramer CJH; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
  • Jobsen JJ; Department of Radiation Oncology, Medisch Spectrum Twente, Enschede, the Netherlands.
  • Jürgemlienk-Schulz I; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Lutgens L; MAASTRO Clinic, Maastricht, the Netherlands.
  • Mens JW; Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Haverkort MAD; Radiotherapiegroep Arnhem, Arnhem, the Netherlands.
  • Slot A; Radiotherapeutic Institute Friesland, Leeuwarden, the Netherlands.
  • Nout RA; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands.
  • Oosting J; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
  • Carlson J; Department of Pathology, University of Southern California, Los Angeles.
  • Howitt BE; Department of Pathology, Stanford University School of Medicine, Palo Alto.
  • Ip PPC; Department of Pathology, University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • Lax SF; Department of Pathology, Hospital Graz II, Medical University of Graz, Graz, and Johannes Kepler University, Linz, Austria.
  • McCluggage WG; Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, United Kingdom.
  • Singh N; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
  • McAlpine JN; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, Canada.
  • Creutzberg CL; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands.
  • Horeweg N; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands.
  • Gilks CB; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
  • Bosse T; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Clin Cancer Res ; 29(23): 4949-4957, 2023 12 01.
Article em En | MEDLINE | ID: mdl-37773079
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias do Endométrio / Carcinoma Endometrioide Tipo de estudo: Prognostic_studies Limite: Female / Humans País/Região como assunto: America do norte Idioma: En Revista: Clin Cancer Res Assunto da revista: NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias do Endométrio / Carcinoma Endometrioide Tipo de estudo: Prognostic_studies Limite: Female / Humans País/Região como assunto: America do norte Idioma: En Revista: Clin Cancer Res Assunto da revista: NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Canadá