Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study
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 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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 21, 2018
- Source ID
- 10.1002/cjp2.109
Entities
People
- Aleksandra Gentry‐maharaj
- Alice S. Whittemore
- Alicia Cazorla‐jiménez
- Aline Talhouk
- Allan Jensen
- Andreas D. Hartkopf
- Andrew Berchuck
- Anna deFazio
- Annette Staebler
- Anthony Swerdlow
- Aocs Group
- Audrey Jung
- Beth Karlan
- Brenda Y. Hernandez
- Catherine J Kennedy
- Cezary Cybulski
- Chen Wang
- Chloe Karpinskyj
- Christine Chow
- David D. Bowtell
- David G. Huntsman
- Ellen L Goode
- Emma Hatfield
- Esther Herpel
- Estrid Høgdall
- Fady Mina
- Florin Andrei Taran
- Frances Daley
- Frances Wang
- Francesmary Modugno
- Francisco J. Candido Dos Reis
- Gregg S Nelson
- Helen Steed
- Holly R Harris
- Hugh Luk
- Jacek Gronwald
- James D Brenton
- Jan Lubinski
- Jana Pasternak
- Javier Benitez
- Jennifer A Doherty
- Jennifer Alsop
- Jennifer M. Koziak
- Jenny Chang‐claude
- Jenny Lester
- Jesús García‐donas
- Joellen M. Schildkraut
- José Palacios
- Joy Hendley
- Jurandyr M. De Andrade
- Kathryn Alsop
- Kirsten B. Moysich
- Linda E Kelemen
- Linda S. Cook
- Lynne R. Wilkens
- Marc T. Goodman
- Maria P. Intermaggio
- Martin Köbel
- Martin Widschwendter
- Mary Anne Rossing
- María J. García
- Melissa C. Larson
- Mercedes Jimenez‐linan
- Micheal E Carney
- Micheal E Jones
- Micheal S Anglesio
- Mitul Shah
- Mona A El‐bahrawy
- Montserrat García‐closas
- Oleg Oszurek
- Pamela J. Thompson
- Paul D. Pharoah
- Paul R. Harnett
- Penny Coulson
- Peter A. Fasching
- Peter F. Rambau
- Peter Sinn
- Prafull Ghatage
- Qin Wang
- Raghwa Sharma
- Robert P. Edwards
- Robert Vierkant
- Roberta B. Ness
- Sabine Behrens
- Sara Y. Brucker
- Sebastian M. Armasu
- Sian Fereday
- Simon A Gayther
- Stacey J Winham
- Stefan Kommoss
- Susan J. Ramus
- Susanna Hernando Polo
- Susanne Krüger Kjaer
- Susha Deen
- Tomasz Huzarski
- Usha Menon
- Weiva Sieh
Organizations
- Alberta Health Services
- Brunel University London
- Canadian Institutes of Health Research
- Cancer Institute of New South Wales
- Cancer Research Society
- Cancer Research UK
- Cedars-Sinai Medical Center
- Danish Cancer Society
- Duke University
- Fred Hutchinson Cancer Center
- Friedrich-Alexander-Universität Erlangen-Nürnberg
- Garvan Institute of Medical Research
- German Cancer Research Center
- HM Hospitales
- Heidelberg University
- Hospital Universitario
- Icahn School of Medicine at Mount Sinai
- Imperial College London
- Institute of Cancer Research
- Karolinska Institutet
- Magee-Womens Research Institute
- Mayo Clinic
- Mayo Foundation for Medical Education and Research
- Medical University of South Carolina
- Ministry of Economy, Industry and Competitiveness
- Minnesota Ovarian Cancer Alliance
- National Cancer Institute
- National Center for Advancing Translational Sciences
- National Center for Oncological Research
- National Institutes of Health
- Peter MacCallum Cancer Centre
- Pomeranian Medical University
- Queen's Medical Centre
- Roswell Park Comprehensive Cancer Center
- Royal Alexandra Hospital, Edmonton
- Stanford University
- Tübingen University Hospital
- United States Army Medical Research and Development Command
- United States Department of Defense
- University College London
- University Hospital Heidelberg
- University of Alcalá
- University of British Columbia
- University of Calgary
- University of California, Los Angeles
- University of Cambridge
- University of Copenhagen
- University of Hawaiʻi System
- University of Melbourne
- University of New Mexico
- University of New South Wales
- University of Pittsburgh
- University of Pittsburgh School of Medicine
- University of Southern California
- University of Sydney
- University of Texas at Austin
- University of Tübingen
- University of Utah
- University of Virginia
- University of Washington
- Western Sydney University
- Westmead Hospital