Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium.
| Title: | Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium. |
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| Authors: | Martins FC; Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, England.; Experimental Medicine Initiative, University of Cambridge, Cambridge, England.; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, England.; Couturier DL; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, England.; Paterson A; Department of Histopathology, Addenbrookes Hospital, Cambridge, England.; Karnezis AN; Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA, USA.; Chow C; OVCARE, Vancouver Coastal Health Research Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.; Nazeran TM; Department of Molecular Oncology and Department of Pathology and Laboratory Medicine, BC Cancer Research Centre, BC Cancer, Vancouver, BC, Canada.; Odunsi A; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.; Gentry-Maharaj A; MRC CTU, Institute of Clinical Trials and Methodology, University College London, London, England.; Vrvilo A; Department of Ob/Gyn, Oregon Health & Science University, Portland, OR, USA.; Hein A; Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.; Talhouk A; Department of Molecular Oncology and Department of Pathology and Laboratory Medicine, BC Cancer Research Centre, BC Cancer, Vancouver, BC, Canada.; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.; Department of Molecular Oncology, BC Cancer Research Centre, BC Cancer, Vancouver, BC, Canada.; Osorio A; Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Hartkopf AD; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany.; Brooks-Wilson A; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.; DeFazio A; Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.; Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia.; Fischer A; Institute of Pathology, Tübingen University Hospital, Tübingen, Germany.; Hartmann A; Institute of Pathology, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.; Hernandez BY; Cancer Center, University of Hawaii, Honolulu, HI, USA.; McCauley BM; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.; Karpinskyj C; MRC CTU, Institute of Clinical Trials and Methodology, University College London, London, England.; de Sousa CB; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Høgdall C; Department of Gynaecology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100, København, Denmark.; Tiezzi DG; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Herpel E; NCT Tissue Bank, National Center for Tumour Diseases, Heidelberg, Germany.; Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.; Taran FA; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany.; Modugno F; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Keeney G; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.; Nelson G; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Steed H; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Royal Alexandra Hospital, Edmonton, AB, Canada.; Song H; Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, England.; Luk H; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.; Benitez J; Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Alsop J; Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, England.; Koziak JM; Alberta Health Services-Cancer Care, Calgary, AB, Canada.; Lester J; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Rothstein JH; 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.; de Andrade JM; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Lundvall L; Department of Gynaecology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100, København, Denmark.; Paz-Ares L; Spanish National Cancer Research Center, CNIO Lung Cancer Clinical Research Unit, New York, NY, USA.; Robles-Díaz L; Familial Cancer Unit and Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.; Wilkens LR; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.; Garcia MJ; Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Intermaggio MP; School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.; Alcaraz ML; Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, England.; Brett MA; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.; Beckmann MW; Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.; Jimenez-Linan M; Department of Histopathology, Addenbrookes Hospital, Cambridge, England.; Anglesio M; OVCARE, Vancouver Coastal Health Research Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.; Department of Molecular Oncology and Department of Pathology and Laboratory Medicine, BC Cancer Research Centre, BC Cancer, Vancouver, BC, Canada.; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.; Carney ME; John A. Burns School of Medicine, Department of Obstetrics and Gynecology, University of Hawaii, Honolulu, HI, USA.; Schneider M; Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.; Traficante N; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.; Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.; Pejovic N; School of Medicine, St. Louis University, St. Louis, MO, 63103, USA.; Singh N; Department of Cellular Pathology, Barts Health National Health Service Trust, London, England.; Le N; Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC, Canada.; Sinn P; Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.; Ghatage P; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Erber R; Institute of Pathology, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.; Edwards R; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Vierkant R; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.; Ness RB; University of Texas School of Public Health, Houston, TX, USA.; Leung S; OVCARE, Vancouver Coastal Health Research Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.; Orsulic S; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Brucker SY; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany.; Kaufmann SH; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.; Fereday S; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.; Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.; Gayther S; Cedars-Sinai Center for Bioinformatics and Functional Genomics, Los Angeles, CA, USA.; Winham SJ; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.; Kommoss S; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany.; Pejovic T; Department of Ob/Gyn, Oregon Health & Science University, Portland, OR, USA.; Longacre TA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; McGuire V; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA.; Rhenius V; Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, England.; Sieh W; 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.; Shvetsov YB; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.; Department of Pathology, University of Melbourne, Melbourne, VIC, Australia.; Whittemore AS; Department of Health Research and Policy and Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.; Staebler A; Institute of Pathology, Tübingen University Hospital, Tübingen, Germany.; Karlan BY; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Rodriguez-Antona C; Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III Madrid, Madrid, Spain.; Bowtell DD; Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Parkville, VIC, Australia.; The Garvan Institute, Sydney, NSW, Australia.; Goode EL; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.; Høgdall E; Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.; Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.; Cancer Genomics Program, Research Department, Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.; Candido Dos Reis FJ; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Gronwald J; International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.; Chang-Claude J; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Moysich KB; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.; Kelemen LE; Department of Public Health Sciences, Medical University of South Carolina and Hollings Cancer Center, Charleston, SC, USA.; Cook LS; Division of Epidemiology, Biostatistics and Preventative Medicine, University of New Mexico, Albuquerque, NM, USA.; Goodman MT; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Fasching PA; Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.; David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, 90095, USA.; Crawford R; Division of Oncology, Addenbrookes Hospital, Cambridge, England.; Deen S; Department of Histopathology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, England.; Menon U; MRC CTU, Institute of Clinical Trials and Methodology, University College London, London, England.; Huntsman DG; OVCARE, Vancouver Coastal Health Research Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.; Department of Molecular Oncology and Department of Pathology and Laboratory Medicine, BC Cancer Research Centre, BC Cancer, Vancouver, BC, Canada.; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.; Department of Molecular Oncology, BC Cancer Research Centre, BC Cancer, Vancouver, BC, Canada.; Köbel M; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.; Ramus SJ; School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.; The Garvan Institute, Sydney, NSW, Australia.; Pharoah PDP; Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, England. pp10001@medschl.cam.ac.uk.; Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Worts Causeway, Cambridge, England. pp10001@medschl.cam.ac.uk.; Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, England. pp10001@medschl.cam.ac.uk.; Brenton JD; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, England. james.brenton@cruk.cam.ac.uk.; Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, England. james.brenton@cruk.cam.ac.uk.; Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, England. james.brenton@cruk.cam.ac.uk. |
| Source: | British journal of cancer [Br J Cancer] 2020 Sep; Vol. 123 (5), pp. 793-802. Date of Electronic Publication: 2020 Jun 18. |
| Publication Type: | Journal Article; Multicenter Study; Observational Study |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK; Original Publication: London, Lewis. |
| MeSH Terms: | PTEN Phosphohydrolase/*biosynthesis; Adenocarcinoma, Clear Cell/enzymology ; Adenocarcinoma, Clear Cell/mortality ; Adenocarcinoma, Clear Cell/pathology ; Biomarkers, Tumor/biosynthesis ; Biomarkers, Tumor/genetics ; Carcinoma, Ovarian Epithelial/enzymology ; Carcinoma, Ovarian Epithelial/genetics ; Carcinoma, Ovarian Epithelial/mortality ; Carcinoma, Ovarian Epithelial/pathology ; Ovarian Neoplasms/enzymology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/pathology ; PTEN Phosphohydrolase/deficiency ; PTEN Phosphohydrolase/genetics ; Receptors, Androgen/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Tumor Suppressor Proteins/biosynthesis ; Tumor Suppressor Proteins/deficiency ; Age Factors ; Cohort Studies ; Down-Regulation ; Female ; Gene Knockout Techniques ; Humans ; Middle Aged ; Neoplasm Staging ; Prospective Studies ; Tissue Array Analysis |
| 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 |
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| Grant Information: | 24267 United Kingdom CRUK_ Cancer Research UK; P50 CA159981 United States CA NCI NIH HHS; MC_UU_12023/20 United Kingdom MRC_ Medical Research Council; 15601 United Kingdom CRUK_ Cancer Research UK; 22905 United Kingdom CRUK_ Cancer Research UK; P30 CA071789 United States CA NCI NIH HHS; P50 CA136393 United States CA NCI NIH HHS |
| Substance Nomenclature: | 0 (AR protein, human); 0 (Biomarkers, Tumor); 0 (Receptors, Androgen); 0 (Receptors, Estrogen); 0 (Receptors, Progesterone); 0 (Tumor Suppressor Proteins); EC 3.1.3.67 (PTEN Phosphohydrolase); EC 3.1.3.67 (PTEN protein, human) |
| Entry Date(s): | Date Created: 20200620 Date Completed: 20210331 Latest Revision: 20250904 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7463007 |
| DOI: | 10.1038/s41416-020-0900-0 |
| PMID: | 32555365 |
| Database: | MEDLINE |
Journal Article; Multicenter Study; Observational Study