Journal article

Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study

Peter F Rambau, Robert A Vierkant, Maria P Intermaggio, Linda E Kelemen, Marc T Goodman, Esther Herpel, Paul D Pharoah, Stefan Kommoss, Mercedes Jimenez-Linan, Beth Y Karlan, Aleksandra Gentry-Maharaj, Usha Menon, Susanna Hernando Polo, Francisco J Candido dos Reis, Jennifer Anne Doherty, Simon A Gayther, Raghwa Sharma, Melissa C Larson, Paul R Harnett, Emma Hatfield Show all

JOURNAL OF PATHOLOGY CLINICAL RESEARCH | WILEY | Published : 2018

Abstract

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 o..

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Grants

Awarded by NCI/NIH


Awarded by U.S. Army Medical Research and Materiel Command


Awarded by NHMRC


Awarded by National Health and Medical Research Council of Australia


Awarded by United States Department of Defence (DoD) Ovarian Cancer Transitional Leverage Award


Awarded by Ministerio de Economia y Competitividad


Awarded by National Cancer Institute of the National Institutes of Health


Awarded by Department of Defense


Awarded by NCI


Awarded by National Center for Advancing Translational Sciences (NCATS)


Awarded by Danish Cancer Society


Awarded by Cancer Research UK


Awarded by Canadian Institutes of Health Research grant


Awarded by NIH/NCI


Awarded by Cancer Institute NSW


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by Canadian Institutes of Health Research


Awarded by Cancer Research Society


Awarded by CLS Internal Research


Awarded by Instituto de Salud Carlos III


Awarded by German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research


Awarded by US National Institutes of Health


Awarded by American Cancer Society Early Detection Professorship


Awarded by Danish Cancer Society, Copenhagen, Denmark


Awarded by National Institutes of Health


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Funding Acknowledgements

We would like to thank all of the women who participated in these research programs. We thank Marjorie J. Riggan (OCAC) for coordination. Acknowledgements for individual studies: The AOCS gratefully acknowledges additional support from S. Boldeman, the Agar family, Ovarian Cancer Action (UK), Ovarian Cancer Australia and the Peter MacCallum Foundation. The AOCS also acknowledges the cooperation of the participating institutions in Australia and acknowledges the contribution of the study nurses, research assistants and all clinical and scientific collaborators to the study. The complete AOCS Study Group can be found at www.aocstudy.org. AOV: We thank Mie Konno, Michelle Darago, Faye Chambers. BGS: We thank Breast Cancer Now and the Institute of Cancer Research for support and funding of the Generations Study, Ovarian Cancer Action for funding of work on ovarian cancer within the Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study and Professor Robert Brown for advice and help. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. CAL: We thank Taryn Burghardt for study coordination and Thomas Kryton (BFA, digital imaging specialist for Calgary Laboratory Services) for creating figures. GER: tissue samples were provided by the tissue bank of the National Center for Tumor Diseases (NCT, Heidelberg, Germany) in accordance with the regulations of the tissue bank and the approval of the ethics committee of the University of Heidelberg. SEA: SEARCH team, Craig Luccarini, Caroline Baynes, Don Conroy. UKO: We particularly thank I. Jacobs, E. Wozniak, A. Ryan, J. Ford and N. Balogun. WMH: We thank the Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group. Peter F. Rambau was supported by a Thomas E. Feasby PhD student fund. NCI/NIH R01CA172404 to Susan J Ramus. Funding for individual studies: AOC: The Australian Ovarian Cancer Study was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Foundation of Western Australia, The Cancer Council Tasmania and the NHMRC (ID400413 and ID400281). Professor David Bowtell is supported by the National Health and Medical Research Council of Australia (NHMRC; APP1092856) and the United States Department of Defence (DoD) Ovarian Cancer Transitional Leverage Award (W81XWH-12-1-0104); AOV: Canadian Institutes of Health Research (MOP-86727).; BAV: ELAN Funds of the University of Erlangen-Nuremberg; CAL: Cancer Research Society (19319) and CLS Internal Research support RS11-508; CNI: Instituto de Salud Carlos III (PI 12/01319); Ministerio de Economia y Competitividad (SAF2012); DOV: NCI/NIH R01CA168758, and NCI/NIH R01CA168758. Huntsman Cancer Foundation and the National Cancer Institute of the National Institutes of Health under Award Number P30CA042014.The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH; GER: German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01GB9401) and the German Cancer Research Center (DKFZ); HAW: US National Institutes of Health (R01-CA58598, N01-CN-55424 and N01-PC-67001); HOP: Department of Defense (DAMD17-02-1-0669) and NCI (K07-CA080668, R01-CA95023, P50-CA159981, MO1-RR000056, R01-CA126841); LAX: American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124; MAL: NCI R01-CA61107, research grant 9422252 from the Danish Cancer Society, Copenhagen, Denmark; and the Mermaid I project; MAY: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; SEA: Cancer Research UK C490/A16561, the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Cambridge Cancer Centre. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. POC: Pomeranian Medical University; TVA: This work was supported by Canadian Institutes of Health Research grant (MOP-86727) and by NIH/NCI 1 R01CA160669-01A1; UKO: The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre; VAN: The Janet D. Cottrelle Foundation Scholars fund provides support to M.S. Anglesio. OVCARE receives core funding from The BC Cancer Foundation and the VGH and UBC Hospital Foundation. WMH: National Health and Medical Research Council of Australia, Enabling Grants ID 310670 and ID 628903. Cancer Institute NSW Grants 12/RIG/1-17 and 15/RIG/1-16.