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MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma.
Kang, Eun Young; Millstein, Joshua; Popovic, Gordana; Meagher, Nicola S; Bolithon, Adelyn; Talhouk, Aline; Chiu, Derek S; Anglesio, Michael S; Leung, Betty; Tang, Katrina; Lambie, Neil; Pavanello, Marina; Da-Anoy, Annalyn; Lambrechts, Diether; Loverix, Liselore; Olbrecht, Siel; Bisinotto, Christiani; Garcia-Donas, Jesus; Ruiz-Llorente, Sergio; Yagüe-Fernandez, Monica; Edwards, Robert P; Elishaev, Esther; Olawaiye, Alexander; Taylor, Sarah; Ataseven, Beyhan; du Bois, Andreas; Harter, Philipp; Lester, Jenny; Høgdall, Claus K; Armasu, Sebastian M; Huang, Yajue; Vierkant, Robert A; Wang, Chen; Winham, Stacey J; Heublein, Sabine; Kommoss, Felix K F; Cramer, Daniel W; Sasamoto, Naoko; van-Wagensveld, Lilian; Lycke, Maria; Mateoiu, Constantina; Joseph, Janine; Pike, Malcolm C; Odunsi, Kunle; Tseng, Chiu-Chen; Pearce, Celeste L; Bilic, Sanela; Conrads, Thomas P; Hartmann, Arndt; Hein, Alexander.
Afiliação
  • Kang EY; Department of Pathology and Laboratory Medicine, Foothills Medical Center, University of Calgary, Calgary, AB, Canada.
  • Millstein J; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Popovic G; Mark Wainwright Analytical Centre, Stats Central, University of New South Wales Sydney, Sydney, Australia.
  • Meagher NS; School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
  • Bolithon A; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, NSW, Australia.
  • Talhouk A; School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
  • Chiu DS; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, NSW, Australia.
  • Anglesio MS; British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, BC, Canada.
  • Leung B; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
  • Tang K; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
  • Lambie N; British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, BC, Canada.
  • Pavanello M; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
  • Da-Anoy A; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
  • Lambrechts D; Histopathology/ISH Core Facility, Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Loverix L; Prince of Wales Clinical School, University of NSW Sydney, Sydney, NSW, Australia.
  • Olbrecht S; Department of Anatomical Pathology, Prince of Wales Hospital, Sydney, Australia.
  • Bisinotto C; NSW Health Pathology, Prince of Wales Hospital, Sydney, Australia.
  • Garcia-Donas J; Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, Australia.
  • Ruiz-Llorente S; Department of Pathology and Laboratory Medicine, Foothills Medical Center, University of Calgary, Calgary, AB, Canada.
  • Yagüe-Fernandez M; VIB Center for Cancer Biology, Leuven, Belgium.
  • Edwards RP; Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium.
  • Elishaev E; Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.
  • Olawaiye A; Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.
  • Taylor S; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Ataseven B; HM Sanchinarro Centro Integral Oncológico Clara Campal, University Hospital, Madrid, Spain.
  • du Bois A; HM Sanchinarro Centro Integral Oncológico Clara Campal, University Hospital, Madrid, Spain.
  • Harter P; HM Sanchinarro Centro Integral Oncológico Clara Campal, University Hospital, Madrid, Spain.
  • Lester J; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Høgdall CK; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Armasu SM; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Huang Y; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Vierkant RA; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen, Germany.
  • Wang C; Department of Gynecology and Obstetrics, Ludwig Maximilian University of Munich, Munich, Germany.
  • Winham SJ; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen, Germany.
  • Heublein S; Department of Gynecology and Gynecological Oncology, Dr. Horst-Schmidt Klinik Wiesbaden, Wiesbaden, Germany.
  • Kommoss FKF; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen, Germany.
  • Cramer DW; Department of Gynecology and Gynecological Oncology, Dr. Horst-Schmidt Klinik Wiesbaden, Wiesbaden, Germany.
  • Sasamoto N; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
  • van-Wagensveld L; Department of Gynaecology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
  • Lycke M; Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA.
  • Mateoiu C; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Joseph J; Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA.
  • Pike MC; Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
  • Odunsi K; Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
  • Tseng CC; Department of Obstetrics and Gynecology, University Hospital Heidelberg, Heidelberg, Germany.
  • Pearce CL; Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
  • Bilic S; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Conrads TP; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Hartmann A; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Hein A; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
Virchows Arch ; 480(4): 855-871, 2022 Apr.
Article em En | MEDLINE | ID: mdl-34782936
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cistadenocarcinoma Seroso / Componente 3 do Complexo de Manutenção de Minicromossomo Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Virchows Arch Assunto da revista: BIOLOGIA MOLECULAR / PATOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cistadenocarcinoma Seroso / Componente 3 do Complexo de Manutenção de Minicromossomo Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Virchows Arch Assunto da revista: BIOLOGIA MOLECULAR / PATOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Canadá