Evidence map›Paper›PMID 34782936›Full record

ArticleVirchows Archiv : an international journal of pathology2022

MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma.

Eun Young Kang, Joshua Millstein, Gordana Popovic, Nicola S Meagher, Adelyn Bolithon, Aline Talhouk, Derek S Chiu, Michael S Anglesio, Betty Leung, Katrina Tang and 104 more

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

Article in Virchows Archiv : an international journal of pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

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  8. Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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  11. Concurrent RB1 loss andmedRxiv : the preprint server for health sciences · 2023
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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

114 authors at 20 institutions in 12 countries.

Eun Young KangDepartment of Pathology and Laboratory Medicine, Foothills Medical Center, University of Calgary, Calgary, AB, Canada.
Joshua MillsteinDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Gordana PopovicMark Wainwright Analytical Centre, Stats Central, University of New South Wales Sydney, Sydney, Australia.
Nicola S MeagherSchool of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
Adelyn BolithonSchool of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
Aline TalhoukBritish Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, BC, Canada.
Derek S ChiuBritish Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, BC, Canada.
Michael S AnglesioDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Betty LeungPrince of Wales Clinical School, University of NSW Sydney, Sydney, NSW, Australia.
Katrina TangDepartment of Anatomical Pathology, Prince of Wales Hospital, Sydney, Australia.
Neil LambieNSW Health Pathology, Prince of Wales Hospital, Sydney, Australia.
Marina PavanelloCentre for Cancer Research, The Westmead Institute for Medical Research, Westmead, Australia.
Annalyn Da-AnoyDepartment of Pathology and Laboratory Medicine, Foothills Medical Center, University of Calgary, Calgary, AB, Canada.
Diether LambrechtsVIB Center for Cancer Biology, Leuven, Belgium.
Liselore LoverixDivision of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.
Siel OlbrechtDivision of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.
Christiani BisinottoDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Jesus Garcia-DonasHM Sanchinarro Centro Integral Oncológico Clara Campal, University Hospital, Madrid, Spain.
Sergio Ruiz-LlorenteHM Sanchinarro Centro Integral Oncológico Clara Campal, University Hospital, Madrid, Spain.
Monica Yagüe-FernandezHM Sanchinarro Centro Integral Oncológico Clara Campal, University Hospital, Madrid, Spain.
Robert P EdwardsDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Esther ElishaevDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Alexander OlawaiyeDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sarah TaylorDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Beyhan AtasevenDepartment of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen, Germany.
Andreas du BoisDepartment of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen, Germany.
Philipp HarterDepartment of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen, Germany.
Jenny LesterDepartment of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Claus K HøgdallDepartment of Gynaecology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Sebastian M ArmasuDepartment of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA.
Yajue HuangDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Robert A VierkantDepartment of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA.
Chen WangDepartment of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
Stacey J WinhamDepartment of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
Sabine HeubleinDepartment of Obstetrics and Gynecology, University Hospital Heidelberg, Heidelberg, Germany.
Felix K F KommossInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Daniel W CramerDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Naoko SasamotoObstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Lilian van-WagensveldDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
Maria LyckeDepartment of Obstetrics and Gynecology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
Constantina MateoiuDepartment of Pathology and Cytology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
Janine JosephDivision of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
Malcolm C PikeDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Kunle OdunsiDepartment of Oncology, University of Chicago, Chicago, IL, USA.
Chiu-Chen TsengDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Celeste L PearceDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Sanela BilicDepartment of Gynaecological Oncology, St John of God Subiaco Hospital, Subiaco, Australia.
Thomas P ConradsWomen's Health Integrated Research Center, Women's Service Line, Inova Health System, Falls Church, VA, USA.
Arndt HartmannInstitute of Pathology, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen-Nürnberg, Germany.
Alexander HeinDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.
Michael E JonesDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Yee LeungDivision of Obstetrics and Gynaecology, Faculty of Health and Medical Sciences, University of Western Australia, Crawley, WA, Australia.
Matthias W BeckmannDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.
Matthias RuebnerDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.
Minouk J SchoemakerDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Kathryn L TerryDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Mona A El-BahrawyDepartment of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Penny CoulsonDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
John L EtterDivision of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
Katherine LaVigne-MagerDepartment of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Juergen AndressDepartment of Women's Health, Tübingen University Hospital, Tübingen, Germany.
Marcel GrubeDepartment of Women's Health, Tübingen University Hospital, Tübingen, Germany.
Anna FischerInstitute of Pathology, Tübingen University Hospital, Tübingen, Germany.
Nina NeudeckInstitute of Pathology, Tübingen University Hospital, Tübingen, Germany.
Greg RobertsonSchool of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
Rhonda FarrellPrince of Wales Private Hospital, Randwick, Australia.
Ellen BarlowGynaecological Cancer Centre, Royal Hospital for Women, Sydney, Australia.
Carmel QuinnMark Wainwright Analytical Centre, Stats Central, University of New South Wales Sydney, Sydney, Australia.
Anusha HettiaratchiUNSW Biorepository, Mark Wainwright Analytical Centre, University of New South Wales Sydney, Sydney, Australia.
Yovanni CasablancaUniformed Services University of the Health Sciences, USAF, Bethesda, MD, USA.
Ramona ErberInstitute of Pathology, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen-Nürnberg, Germany.
Colin J R StewartSchool for Women's and Infants' Health, University of Western Australia, Perth, Australia.
Adeline TanDivision of Obstetrics and Gynaecology, Faculty of Health and Medical Sciences, University of Western Australia, Crawley, WA, Australia.
Yu YuSchool of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
Jessica BorosCentre for Cancer Research, The Westmead Institute for Medical Research, Westmead, Australia.
Alison H BrandDepartment of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia.
Paul R HarnettThe Crown Princess Mary Cancer Centre Westmead, Sydney-West Cancer Network, Westmead Hospital, Sydney, NSW, Australia.
Catherine J KennedyCentre for Cancer Research, The Westmead Institute for Medical Research, Westmead, Australia.
Nikilyn NevinsCentre for Cancer Research, The Westmead Institute for Medical Research, Westmead, Australia.
Terry MorganDepartment of Pathology, Oregon Health & Science University, Portland, OR, USA.
Peter A FaschingDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.
Ignace VergoteDivision of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.
Anthony J SwerdlowDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Francisco J Candido Dos ReisDepartment of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
G Larry MaxwellWomen's Service Line, Inova Health System, Falls Church, VA, USA.
Susan L NeuhausenDepartment of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Arantzazu Barquin-GarciaHM Sanchinarro Centro Integral Oncológico Clara Campal, University Hospital, Madrid, Spain.
Francesmary ModugnoDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Kirsten B MoysichDivision of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
Philip J CrowePrince of Wales Clinical School, University of NSW Sydney, Sydney, NSW, Australia.
Akira HirasawaDepartment of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Florian HeitzDepartment of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen, Germany.
Beth Y KarlanDepartment of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Ellen L GoodeDepartment of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
Peter SinnInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Hugo M HorlingsDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
Estrid HøgdallDepartment of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Karin SundfeldtDepartment of Obstetrics and Gynecology, Sahlgrenska Center for Cancer Research, Gothenburg University, Gothenburg, Sweden.
Stefan KommossDepartment of Women's Health, Tübingen University Hospital, Tübingen, Germany.
Annette StaeblerInstitute of Pathology, Tübingen University Hospital, Tübingen, Germany.
Anna H WuDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Paul A CohenDivision of Obstetrics and Gynaecology, Faculty of Health and Medical Sciences, University of Western Australia, Crawley, WA, Australia.
Anna DeFazioCentre for Cancer Research, The Westmead Institute for Medical Research, Westmead, Australia.
Cheng-Han LeeDepartment of Pathology and Laboratory Medicine, University of Alberta, Edmonton, AB, Canada.
Helen SteedDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, Royal Alexandra Hospital, Edmonton, AB, Canada.
Nhu D LeCancer Control Research, BC Cancer, Vancouver, BC, Canada.
Simon A GaytherCenter for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Kate LawrensonDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Women's Cancer Program at the Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Paul D P PharoahDepartment of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
Gottfried KonecnyDepartment of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Linda S CookSchool of Public Health, University of Colorado, Aurora, CO, USA.
Susan J RamusSchool of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
Linda E KelemenBureau of Population Health Data Analytics & Informatics, South Carolina Department of Health and Environmental Control, Columbia, SC, USA.
Martin KöbelDepartment of Pathology and Laboratory Medicine, Foothills Medical Center, University of Calgary, Calgary, AB, Canada. mkoebel@ucalgary.ca.ORCID http://orcid.org/0000-0002-6615-2037
University Children's Hospital Tübingen · DEMayo Clinic in Florida · USUniversitätsklinikum Erlangen · DEUniversity of Pittsburgh · USUniversity of Southern California · USCancer Institute of New South Wales · AUHospital Universitario HM Sanchinarro · ESInstitute of Cancer Research · GBRoswell Park Comprehensive Cancer Center · USUniversity of California, Los Angeles · USBrigham and Women's Hospital · USHeidelberg University · DEHelios Dr. Horst Schmidt Kliniken Wiesbaden · DEKU Leuven · BEPrince of Wales Hospital · AUThe University of Sydney · AUThe University of Western Australia · AUUniversity of Calgary · CAUNSW Sydney · AUWestmead Hospital · AU

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI ELLEN L. GOODE · 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
Relating Molecular Subgroups of Endometriosis-Associated Ovarian Cancers to Survival and RiskR01CA248288 · NCI · MAYO CLINIC ROCHESTER · PI Stacey J Winham · 2021 to 2026
$4.8M
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
OVARIAN CANCER RISK AND SURVIVAL IN BRCA CARRIERSK07CA080668 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MODUGNO, FRANCESMARY · 2000 to 2005
$661k
Cancer Research UK 16561NCI NIH HHS K07 CA080668NCI NIH HHS K07-CA80668NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA047904NCI NIH HHS P50-CA135393NCI NIH HHS P50 CA136393NCI NIH HHS R01 CA095023NCI NIH HHS R01CA095023NCI NIH HHS R01 CA126841NCI NIH HHS R01 CA172404NCI NIH HHS R01CA172404NCI NIH HHS R01 CA248288NCI NIH HHS R01-CA248288NCRR NIH HHS M01 RR000056NCRR NIH HHS MO1- RR000056
6 · The paper itself

Abstract

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.

Indexed as

Cystadenocarcinoma, SerousMinichromosome Maintenance Complex Component 3Ovarian NeoplasmsBiomarkers, TumorCell ProliferationFemaleHumansKi-67 AntigenRNA, MessengerSurvival RateBiomarkers, TumorKi-67 AntigenMCM3 protein, humanMinichromosome Maintenance Complex Component 3RNA, MessengerHigh-grade serous carcinomaMCM3Proliferation

Identifiers

PMID34782936
PMCPMC9035053
OpenAlexW3212610509

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