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CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.
Kang, Eun-Young; Weir, Ashley; Meagher, Nicola S; Farrington, Kyo; Nelson, Gregg S; Ghatage, Prafull; Lee, Cheng-Han; Riggan, Marjorie J; Bolithon, Adelyn; Popovic, Gordana; Leung, Betty; Tang, Katrina; Lambie, Neil; Millstein, Joshua; Alsop, Jennifer; Anglesio, Michael S; Ataseven, Beyhan; Barlow, Ellen; Beckmann, Matthias W; Berger, Jessica; Bisinotto, Christiani; Bösmüller, Hans; Boros, Jessica; Brand, Alison H; Brooks-Wilson, Angela; Brucker, Sara Y; Carney, Michael E; Casablanca, Yovanni; Cazorla-Jiménez, Alicia; Cohen, Paul A; Conrads, Thomas P; Cook, Linda S; Coulson, Penny; Courtney-Brooks, Madeleine; Cramer, Daniel W; Crowe, Philip; Cunningham, Julie M; Cybulski, Cezary; Darcy, Kathleen M; El-Bahrawy, Mona A; Elishaev, Esther; Erber, Ramona; Farrell, Rhonda; Fereday, Sian; Fischer, Anna; García, María J; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Gilks, C Blake; Grube, Marcel.
Afiliação
  • Kang EY; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, Alberta, Canada.
  • Weir A; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Meagher NS; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Farrington K; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Nelson GS; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Ghatage P; The Daffodil Centre, The University of Sydney, A Joint Venture With Cancer Council NSW, Sydney, New South Wales, Australia.
  • Lee CH; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, Alberta, Canada.
  • Riggan MJ; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
  • Bolithon A; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
  • Popovic G; Department of Pathology and Laboratory Medicine, University of Alberta, Edmonton, Alberta, Canada.
  • Leung B; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina, USA.
  • Tang K; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Lambie N; School of Women's and Children's Health, Faculty of Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Millstein J; Stats Central, Mark Wainwright Analytical Centre, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Alsop J; Prince of Wales Clinical School, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Anglesio MS; Department of Anatomical Pathology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
  • Ataseven B; Canterbury Health Laboratories, Christchurch, New Zealand.
  • Barlow E; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Beckmann MW; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
  • Berger J; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.
  • Bisinotto C; British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, British Columbia, Canada.
  • Bösmüller H; Department of Gynecology and Gynecologic Oncology, Evangelische Kliniken Essen-Mitte (KEM), Essen, Germany.
  • Boros J; Department of Obstetrics and Gynecology, Ludwig Maximilian University Munich, Munich, Germany.
  • Brand AH; Gynaecological Cancer Centre, Royal Hospital for Women, Sydney, New South Wales, Australia.
  • Brooks-Wilson A; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
  • Brucker SY; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Carney ME; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Casablanca Y; Institute of Pathology and Neuropathology, Tuebingen University Hospital, Tuebingen, Germany.
  • Cazorla-Jiménez A; Centre for Cancer Research, The Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Cohen PA; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
  • Conrads TP; Discipline of Obstetrics and Gynaecology, The University of Sydney, Sydney, New South Wales, Australia.
  • Cook LS; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
  • Coulson P; Discipline of Obstetrics and Gynaecology, The University of Sydney, Sydney, New South Wales, Australia.
  • Courtney-Brooks M; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.
  • Cramer DW; Department of Women's Health, Tuebingen University Hospital, Tuebingen, Germany.
  • Crowe P; Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA.
  • Cunningham JM; Uniformed Services of the Health Sciences Gynecologic Cancer Center of Excellence, Bethesda, Maryland, USA.
  • Cybulski C; Pathology Department, Fundación Jiménez Díaz, Madrid, Spain.
  • Darcy KM; Department of Gynaecological Oncology, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia.
  • El-Bahrawy MA; Division of Obstetrics and Gynaecology, Medical School, University of Western Australia, Crawley, Western Australia, Australia.
  • Elishaev E; Women's Health Integrated Research Center, Inova Health System, Falls Church, Virginia, USA.
  • Erber R; Epidemiology, School of Public Health, University of Colorado, Aurora, Colorado, USA.
  • Farrell R; Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
  • Fereday S; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Fischer A; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • García MJ; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Gayther SA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Gentry-Maharaj A; Prince of Wales Clinical School, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Gilks CB; Department of Surgery, Prince of Wales Private Hospital, Randwick, New South Wales, Australia.
  • Grube M; Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Cancer ; 129(5): 697-713, 2023 03 01.
Article em En | MEDLINE | ID: mdl-36572991
ABSTRACT

BACKGROUND:

Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.

METHODS:

Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.

RESULTS:

High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss.

CONCLUSION:

This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Carcinoma / Cistadenocarcinoma Seroso Limite: Female / Humans Idioma: En Revista: Cancer Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Carcinoma / Cistadenocarcinoma Seroso Limite: Female / Humans Idioma: En Revista: Cancer Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Canadá