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Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium.
Martins, Filipe Correia; Couturier, Dominique-Laurent; Paterson, Anna; Karnezis, Anthony N; Chow, Christine; Nazeran, Tayyebeh M; Odunsi, Adekunle; Gentry-Maharaj, Aleksandra; Vrvilo, Aleksandra; Hein, Alexander; Talhouk, Aline; Osorio, Ana; Hartkopf, Andreas D; Brooks-Wilson, Angela; DeFazio, Anna; Fischer, Anna; Hartmann, Arndt; Hernandez, Brenda Y; McCauley, Bryan M; Karpinskyj, Chloe; de Sousa, Christiani B; Høgdall, Claus; Tiezzi, Daniel G; Herpel, Esther; Taran, Florin Andrei; Modugno, Francesmary; Keeney, Gary; Nelson, Gregg; Steed, Helen; Song, Honglin; Luk, Hugh; Benitez, Javier; Alsop, Jennifer; Koziak, Jennifer M; Lester, Jenny; Rothstein, Joseph H; de Andrade, Jurandyr M; Lundvall, Lene; Paz-Ares, Luis; Robles-Díaz, Luis; Wilkens, Lynne R; Garcia, Maria J; Intermaggio, Maria P; Alcaraz, Marie-Lyne; Brett, Mary A; Beckmann, Matthias W; Jimenez-Linan, Mercedes; Anglesio, Michael; Carney, Michael E; Schneider, Michael.
Afiliação
  • Martins FC; Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, England.
  • Couturier DL; Experimental Medicine Initiative, University of Cambridge, Cambridge, England.
  • Paterson A; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, England.
  • Karnezis AN; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, England.
  • Chow C; Department of Histopathology, Addenbrookes Hospital, Cambridge, England.
  • Nazeran TM; Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA, USA.
  • Odunsi A; OVCARE, Vancouver Coastal Health Research Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
  • Gentry-Maharaj A; Department of Molecular Oncology and Department of Pathology and Laboratory Medicine, BC Cancer Research Centre, BC Cancer, Vancouver, BC, Canada.
  • Vrvilo A; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
  • Hein A; MRC CTU, Institute of Clinical Trials and Methodology, University College London, London, England.
  • Talhouk A; Department of Ob/Gyn, Oregon Health & Science University, Portland, OR, USA.
  • Osorio A; Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Hartkopf AD; Department of Molecular Oncology and Department of Pathology and Laboratory Medicine, BC Cancer Research Centre, BC Cancer, Vancouver, BC, Canada.
  • Brooks-Wilson A; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
  • DeFazio A; Department of Molecular Oncology, BC Cancer Research Centre, BC Cancer, Vancouver, BC, Canada.
  • Fischer A; Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Hartmann A; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
  • Hernandez BY; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany.
  • McCauley BM; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.
  • Karpinskyj C; Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
  • de Sousa CB; Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia.
  • Høgdall C; Institute of Pathology, Tübingen University Hospital, Tübingen, Germany.
  • Tiezzi DG; Institute of Pathology, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Herpel E; Cancer Center, University of Hawaii, Honolulu, HI, USA.
  • Taran FA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Modugno F; MRC CTU, Institute of Clinical Trials and Methodology, University College London, London, England.
  • Keeney G; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Nelson G; Department of Gynaecology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100, København, Denmark.
  • Steed H; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Song H; NCT Tissue Bank, National Center for Tumour Diseases, Heidelberg, Germany.
  • Luk H; Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
  • Benitez J; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany.
  • Alsop J; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Koziak JM; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Lester J; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Rothstein JH; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Royal Alexandra Hospital, Edmonton, AB, Canada.
  • de Andrade JM; Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, England.
  • Lundvall L; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Paz-Ares L; Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Robles-Díaz L; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
  • Wilkens LR; Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, England.
  • Garcia MJ; Alberta Health Services-Cancer Care, Calgary, AB, Canada.
  • Intermaggio MP; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Alcaraz ML; Department of Population Health Science and Policy and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Brett MA; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Beckmann MW; Department of Gynaecology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100, København, Denmark.
  • Jimenez-Linan M; Spanish National Cancer Research Center, CNIO Lung Cancer Clinical Research Unit, New York, NY, USA.
  • Anglesio M; Familial Cancer Unit and Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
  • Carney ME; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Schneider M; Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Br J Cancer ; 123(5): 793-802, 2020 09.
Article em En | MEDLINE | ID: mdl-32555365
ABSTRACT

BACKGROUND:

PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.

METHODS:

Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.

RESULTS:

Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio 0.78, 95% CI 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016).

CONCLUSIONS:

PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: PTEN Fosfo-Hidrolase Tipo de estudo: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: PTEN Fosfo-Hidrolase Tipo de estudo: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article