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p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.
Köbel, Martin; Kang, Eun-Young; Weir, Ashley; Rambau, Peter F; Lee, Cheng-Han; Nelson, Gregg S; Ghatage, Prafull; Meagher, Nicola S; Riggan, Marjorie J; Alsop, Jennifer; Anglesio, Michael S; Beckmann, Matthias W; Bisinotto, Christiani; Boisen, Michelle; Boros, Jessica; Brand, Alison H; Brooks-Wilson, Angela; Carney, Michael E; Coulson, Penny; Courtney-Brooks, Madeleine; Cushing-Haugen, Kara L; Cybulski, Cezary; Deen, Suha; El-Bahrawy, Mona A; Elishaev, Esther; Erber, Ramona; Fereday, Sian; Fischer, Anna; Gayther, Simon A; Barquin-Garcia, Arantzazu; Gentry-Maharaj, Aleksandra; Gilks, C Blake; Gronwald, Helena; Grube, Marcel; Harnett, Paul R; Harris, Holly R; Hartkopf, Andreas D; Hartmann, Arndt; Hein, Alexander; Hendley, Joy; Hernandez, Brenda Y; Huang, Yajue; Jakubowska, Anna; Jimenez-Linan, Mercedes; Jones, Michael E; Kennedy, Catherine J; Kluz, Tomasz; Koziak, Jennifer M; Lesnock, Jaime; Lester, Jenny.
Affiliation
  • Köbel M; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
  • Kang EY; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
  • Weir A; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Rambau PF; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Lee CH; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Nelson GS; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
  • Ghatage P; Pathology Department, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania.
  • Meagher NS; Department of Pathology and Laboratory Medicine, University of Alberta, Edmonton, AB, Canada.
  • Riggan MJ; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Alsop J; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Anglesio MS; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.
  • Beckmann MW; The Daffodil Centre, The University of Sydney, a Joint Venture with Cancer Council NSW, Sydney, New South Wales, Australia.
  • Bisinotto C; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA.
  • Boisen M; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Boros J; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
  • Brand AH; British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, BC, Canada.
  • Brooks-Wilson A; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
  • Carney ME; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Coulson P; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Courtney-Brooks M; Centre for Cancer Research, The Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Cushing-Haugen KL; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
  • Cybulski C; Discipline of Obstetrics and Gynaecology, The University of Sydney, Sydney, New South Wales, Australia.
  • Deen S; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
  • El-Bahrawy MA; Discipline of Obstetrics and Gynaecology, The University of Sydney, Sydney, New South Wales, Australia.
  • Elishaev E; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
  • Erber R; Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
  • Fereday S; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Fischer A; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Gayther SA; Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
  • Barquin-Garcia A; Department of Histopathology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Nottingham, UK.
  • Gentry-Maharaj A; Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Hospital, London, UK.
  • Gilks CB; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Gronwald H; Institute of Pathology, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
  • Grube M; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Harnett PR; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Harris HR; Centre for Cancer Research, The Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
  • Hartkopf AD; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Hartmann A; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Hein A; Institute of Pathology and Neuropathology, Tuebingen University Hospital, Tuebingen, Germany.
  • Hendley J; Center for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Hernandez BY; HM Sanchinarro Centro Integral Oncológico Clara Campal, University Hospital, Madrid, Spain.
  • Huang Y; MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK.
  • Jakubowska A; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
  • Jimenez-Linan M; Department of Propaedeutics, Physical Diagnostics and Dental Physiotherapy, Pomeranian Medical University, Szczecin, Poland.
  • Jones ME; Department of Women's Health, Tuebingen University Hospital, Tuebingen, Germany.
  • Kennedy CJ; Discipline of Obstetrics and Gynaecology, The University of Sydney, Sydney, New South Wales, Australia.
  • Kluz T; Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.
  • Koziak JM; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Lesnock J; Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Lester J; Department of Women's Health, Tuebingen University Hospital, Tuebingen, Germany.
J Pathol Clin Res ; 9(3): 208-222, 2023 05.
Article in En | MEDLINE | ID: mdl-36948887
ABSTRACT
Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Carcinoma, Endometrioid Limits: Female / Humans Language: En Journal: J Pathol Clin Res Year: 2023 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Carcinoma, Endometrioid Limits: Female / Humans Language: En Journal: J Pathol Clin Res Year: 2023 Document type: Article Affiliation country: