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Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.
Rambau, Peter F; Vierkant, Robert A; Intermaggio, Maria P; Kelemen, Linda E; Goodman, Marc T; Herpel, Esther; Pharoah, Paul D; Kommoss, Stefan; Jimenez-Linan, Mercedes; Karlan, Beth Y; Gentry-Maharaj, Aleksandra; Menon, Usha; Polo, Susanna Hernando; Candido Dos Reis, Francisco J; Doherty, Jennifer Anne; Gayther, Simon A; Sharma, Raghwa; Larson, Melissa C; Harnett, Paul R; Hatfield, Emma; de Andrade, Jurandyr M; Nelson, Gregg S; Steed, Helen; Schildkraut, Joellen M; Carney, Micheal E; Høgdall, Estrid; Whittemore, Alice S; Widschwendter, Martin; Kennedy, Catherine J; Wang, Frances; Wang, Qin; Wang, Chen; Armasu, Sebastian M; Daley, Frances; Coulson, Penny; Jones, Micheal E; Anglesio, Micheal S; Chow, Christine; de Fazio, Anna; García-Closas, Montserrat; Brucker, Sara Y; Cybulski, Cezary; Harris, Holly R; Hartkopf, Andreas D; Huzarski, Tomasz; Jensen, Allan; Lubinski, Jan; Oszurek, Oleg; Benitez, Javier; Mina, Fady.
Afiliación
  • Rambau PF; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
  • Vierkant RA; Pathology Department, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania.
  • Intermaggio MP; Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
  • Kelemen LE; School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
  • Goodman MT; Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
  • Herpel E; Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Pharoah PD; National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
  • Kommoss S; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Jimenez-Linan M; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Karlan BY; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany.
  • Gentry-Maharaj A; Department of Histopathology, Addenbrookes Hospital, Cambridge, UK.
  • Menon U; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Polo SH; Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK.
  • Candido Dos Reis FJ; Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK.
  • Doherty JA; Medical Oncology Service, Hospital Universitario Funcación Alcorcón, Alcorcón, Spain.
  • Gayther SA; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Sharma R; Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
  • Larson MC; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Harnett PR; Center for Cancer Prevention and Translational Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Hatfield E; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • de Andrade JM; Pathology West ICPMR Westmead, Westmead Hospital, The University of Sydney, Sydney, NSW, Australia.
  • Nelson GS; University of Western Sydney at Westmead Hospital, Westmead, NSW, Australia.
  • Steed H; Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
  • Schildkraut JM; Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
  • Carney ME; The Crown Princess Mary Cancer Centre Westmead, Sydney-West Cancer Network, Westmead Hospital, Sydney, NSW, Australia.
  • Høgdall E; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
  • Whittemore AS; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Widschwendter M; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Kennedy CJ; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Royal Alexandra Hospital, Edmonton, AB, Canada.
  • Wang F; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
  • Wang Q; John A. Burns School of Medicine, Department of Obstetrics and Gynecology, University of Hawaii, Honolulu, HI, USA.
  • Wang C; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
  • Armasu SM; Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
  • Daley F; Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, CA, USA.
  • Coulson P; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
  • Jones ME; Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK.
  • Anglesio MS; Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
  • Chow C; Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia.
  • de Fazio A; Cancer Control and Population Sciences, Duke Cancer Institute, Durham, NC, USA.
  • García-Closas M; Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA.
  • Brucker SY; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Cybulski C; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Harris HR; Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
  • Hartkopf AD; Division of Breast Cancer Research, Institute of Cancer Research, London, UK.
  • Huzarski T; Division of Bioscience, Brunel University, London, UK.
  • Jensen A; Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
  • Lubinski J; Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
  • Oszurek O; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
  • Benitez J; Genetic Pathology Evaluation Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
  • Mina F; Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
J Pathol Clin Res ; 4(4): 250-261, 2018 10.
Article en En | MEDLINE | ID: mdl-30062862
We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Ovario / Cistadenocarcinoma Seroso / Adenocarcinoma Mucinoso / Inhibidor p16 de la Quinasa Dependiente de Ciclina Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Pathol Clin Res Año: 2018 Tipo del documento: Article
Texto completo
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Ovario / Cistadenocarcinoma Seroso / Adenocarcinoma Mucinoso / Inhibidor p16 de la Quinasa Dependiente de Ciclina Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Pathol Clin Res Año: 2018 Tipo del documento: Article