Evidence map›Paper›PMID 30062862›Full record

ArticleThe journal of pathology. Clinical research2018

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 and 87 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of pathology. Clinical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
10.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 98 citations in OpenAlex.

  1. p53 Normal and p53 Abnormal Clear Cell Ovarian Carcinomas: Clinical Characteristics and Biomarker Profiles.International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists · 2026
    Article
  2. p16 Beyond Senescence: Cancer Biology Lessons Applied to Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Cellular origins of mucinous ovarian carcinoma.The Journal of pathology · 2025
    Review
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

97 authors at 20 institutions in 11 countries.

Peter F RambauDepartment of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
Robert A VierkantDepartment of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
Maria P IntermaggioSchool of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
Linda E KelemenDepartment of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
Marc T GoodmanSamuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Esther HerpelNational Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
Paul D PharoahCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Stefan KommossDepartment of Women's Health, Tübingen University Hospital, Tübingen, Germany.
Mercedes Jimenez-LinanDepartment of Histopathology, Addenbrookes Hospital, Cambridge, UK.
Beth Y KarlanWomen's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Aleksandra Gentry-MaharajGynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK.
Usha MenonGynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK.
Susanna Hernando PoloMedical Oncology Service, Hospital Universitario Funcación Alcorcón, Alcorcón, Spain.
Francisco J Candido Dos ReisDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Jennifer Anne DohertyDepartment of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Simon A GaytherDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Raghwa SharmaPathology West ICPMR Westmead, Westmead Hospital, The University of Sydney, Sydney, NSW, Australia.
Melissa C LarsonDepartment of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
Paul R HarnettCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Emma HatfieldDepartment of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
Jurandyr M de AndradeDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Gregg S NelsonDepartment of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Helen SteedDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, Royal Alexandra Hospital, Edmonton, AB, Canada.
Joellen M SchildkrautDepartment of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Micheal E CarneyJohn A. Burns School of Medicine, Department of Obstetrics and Gynecology, University of Hawaii, Honolulu, HI, USA.
Estrid HøgdallDepartment of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Alice S WhittemoreDepartment of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, CA, USA.
Martin WidschwendterGynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK.
Catherine J KennedyCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Frances WangCancer Control and Population Sciences, Duke Cancer Institute, Durham, NC, USA.
Qin WangCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Chen WangDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Sebastian M ArmasuDepartment of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
Frances DaleyDivision of Breast Cancer Research, Institute of Cancer Research, London, UK.
Penny CoulsonDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
Micheal E JonesDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
Micheal S AnglesioDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Christine ChowGenetic Pathology Evaluation Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
Anna de FazioCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Montserrat García-ClosasDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
Sara Y BruckerDepartment of Gynecology and Obstetrics, University of Tübingen, Tübingen, Germany.
Cezary CybulskiDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Holly R HarrisProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Andreas D HartkopfDepartment of Women's Health, Tübingen University Hospital, Tübingen, Germany.
Tomasz HuzarskiDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Allan JensenDepartment of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Jan LubińskiDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Oleg OszurekInternational Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Javier BenitezHuman Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Fady MinaDepartment of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
Annette StaeblerInstitute of Pathology, Tübingen University Hospital, Tübingen, Germany.
Florin Andrei TaranDepartment of Women's Health, Tübingen University Hospital, Tübingen, Germany.
Jana PasternakDepartment of Women's Health, Tübingen University Hospital, Tübingen, Germany.
Aline TalhoukBritish Columbia's Ovarian Cancer Research (OVCARE) Program, Vancouver General Hospital, BC Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
Mary Anne RossingProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Joy HendleyDepartment of Research, Cancer Genomics and Genetics, Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
AOCS GroupPeter MacCallum Cancer Center, Melbourne, VIC, Australia.
Robert P EdwardsOvarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Sian FeredayDepartment of Research, Cancer Genomics and Genetics, Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
Francesmary ModugnoDivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Roberta B NessUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA.
Weiva SiehDepartment of Genetics and Genomic Sciences, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Mona A El-BahrawyDepartment of Histopathology, Imperial College London, Hammersmith Hospital, London, UK.
Stacey J WinhamDepartment of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
Jenny LesterWomen's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Susanne K KjaerDepartment of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Jacek GronwaldDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Peter SinnDepartment of Pathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Peter A FaschingDavid Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, USA.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Kirsten B MoysichDivision of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
David D BowtellDepartment of Research, Cancer Genomics and Genetics, Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
Brenda Y HernandezCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Hugh LukCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Sabine BehrensDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Mitul ShahCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Audrey JungDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Prafull GhatageDepartment of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Jennifer AlsopCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Kathryn AlsopDepartment of Research, Cancer Genomics and Genetics, Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
Jesús García-DonasMedical Oncology Service, HM Hospitales - Centro Integral Oncológico HM Clara Campal, Madrid, Spain.
Pamela J ThompsonSamuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Anthony J SwerdlowDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Chloe KarpinskyjGynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK.
Alicia Cazorla-JiménezPathology Department, Fundación Jiménez Díaz-Quiron Salud, Madrid, Spain.
María J GarcíaHuman Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Susha DeenDepartment of Histopathology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Lynne R WilkensCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
José PalaciosPathology Department, IRYCIS, CIBERONC, Universidad de Alcalá, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Andrew BerchuckDepartment of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Jennifer M KoziakAlberta Health Services-Cancer Care, Calgary, AB, Canada.
James D BrentonCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Linda S CookUniversity of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, NM, USA.
Ellen L GoodeDepartment of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
David G HuntsmanDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Susan J RamusSchool of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
Martin KöbelDepartment of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.ORCID 0000-0002-6615-2037
University of Calgary · CAUniversity of Hawaiʻi at Mānoa · USCedars-Sinai Medical Center · USInstitute of Cancer Research · GBUniversity Children's Hospital Tübingen · DEAlberta Health Services · CAThe University of Sydney · AUBC Cancer Agency · CABreast Cancer Now · GBMayo Clinic · USPomeranian Medical University · PLUniversity of Cambridge · GBUniversity of Pittsburgh · USGerman Cancer Research Center · DEHammersmith Hospital · GBHeidelberg University · DEPeter MacCallum Cancer Centre · AURoswell Park Comprehensive Cancer Center · USSpanish National Cancer Research Centre · ESThe University of Texas MD Anderson Cancer Center · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
University of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI Xin Chen · 1996 to 2026
$56.2M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI Zhenkun Lou · 2009 to 2026
$37.0M
WITHIN SUBJ VARIABILITY IN MEASUREMENTS DRUG METABOL ENZYMES IN HLTY SUBJM01RR000056 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEVINE, ARTHUR S · 1985 to 2006
$29.2M
RPCI-UPCI Ovarian Cancer SPOREP50CA159981 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MOYSICH, KIRSTEN B. · 2013 to 2025
$19.6M
COLLABORATIVE STUDY OF OVARIAN CANCER IN TWO RISK GROUPSR01CA058598 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI GOODMAN, MARC T · 1993 to 2012
$4.6M
Regulatory T Cell Function in Ovarian CancerR01CA126841 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MOYSICH, KIRSTEN B. · 2009 to 2013
$3.0M
Identifying Prognostic Markers and Therapeutic Targets for Serous Ovarian CancerR01CA172404 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI RAMUS, SUSAN J · 2013 to 2017
$2.9M
Inflammation and Ovarian CancerR01CA095023 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BUNKER, CLAREANN H. · 2003 to 2008
$2.7M
Genetic Variation in the NF-kappaB Pathway and Ovarian Cancer EtiologyR01CA122443 · NCI · MAYO CLINIC ROCHESTER · PI GOODE, ELLEN L. · 2007 to 2012
$2.7M
Cancer Research UK 10119Cancer Research UK 16561Cancer Research UK C490/A16561NCATS NIH HHS UL1 TR000124NCI NIH HHS K07 CA080668NCI NIH HHS N01 CA015083NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA042014NCI NIH HHS P30 CA071789NCI NIH HHS P50 CA136393NCI NIH HHS P50 CA159981NCI NIH HHS R01 CA058598NCI NIH HHS R01 CA095023NCI NIH HHS R01 CA122443NCI NIH HHS R01 CA126841NCI NIH HHS R01 CA160669NCI NIH HHS R01 CA168758NCI NIH HHS R01 CA172404NCRR NIH HHS M01 RR000056
6 · The paper itself

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 < 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.

Indexed as

Adenocarcinoma, MucinousAdultAgedCyclin-Dependent Kinase Inhibitor p16Cystadenocarcinoma, SerousFemaleHumansImmunohistochemistryMiddle AgedOvarian NeoplasmsOvaryPrognosisSurvival RateCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16immunocytochemistryovaryRT-QPCR

Identifiers

PMID30062862
PMCPMC6174617
OpenAlexW2886558446

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