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Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.
Weir, Ashley; Kang, Eun-Young; Meagher, Nicola S; Nelson, Gregg S; Ghatage, Prafull; Lee, Cheng-Han; Riggan, Marjorie J; Gentry-Maharaj, Aleksandra; Ryan, Andy; Singh, Naveena; Widschwendter, Martin; Alsop, Jennifer; Anglesio, Michael S; Beckmann, Matthias W; Berger, Jessica; Bisinotto, Christiani; Boros, Jessica; Brand, Alison H; Brenton, James D; Brooks-Wilson, Angela; Carney, Michael E; Cunningham, Julie M; Cushing-Haugen, Kara L; Cybulski, Cezary; Elishaev, Esther; Erber, Ramona; Fereday, Sian; Fischer, Anna; Paz-Ares, Luis; Gayarre, Javier; Gilks, Blake C; Grube, Marcel; Harnett, Paul R; Harris, Holly R; Hartmann, Arndt; Hein, Alexander; Hendley, Joy; Hernandez, Brenda Y; Heublein, Sabine; Huang, Yajue; Huzarski, Tomasz; Jakubowska, Anna; Jimenez-Linan, Mercedes; Kennedy, Catherine J; Kommoss, Felix K F; Koziak, Jennifer M; Kraemer, Bernhard; Le, Nhu D; Lesnock, Jaime; Lester, Jenny.
Afiliación
  • Weir A; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, NSW, Australia.
  • Kang EY; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, NSW, Australia.
  • Meagher NS; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Nelson GS; Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
  • Ghatage P; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, NSW, Australia.
  • Lee CH; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, NSW, Australia.
  • Riggan MJ; The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia.
  • Gentry-Maharaj A; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Ryan A; Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Singh N; Department of Pathology and Laboratory Medicine, University of Alberta, Edmonton, AB, Canada.
  • Widschwendter M; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA.
  • Alsop J; MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK.
  • Anglesio MS; MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK.
  • Beckmann MW; Women's Cancer, Institute for Women's Health, University College London, London, UK.
  • Berger J; Department of Pathology, Barts Health National Health Service Trust, London, UK.
  • Bisinotto C; EUTOPS Institute, University of Innsbruck, Innsbruck, Austria.
  • Boros J; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Brand AH; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
  • Brenton JD; British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, BC, Canada.
  • Brooks-Wilson A; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
  • Carney ME; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Cunningham JM; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Cushing-Haugen KL; Centre for Cancer Research, The Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia.
  • Cybulski C; Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia.
  • Elishaev E; The University of Sydney, Sydney, NSW, Australia.
  • Erber R; Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia.
  • Fereday S; The University of Sydney, Sydney, NSW, Australia.
  • Fischer A; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Paz-Ares L; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
  • Gayarre J; Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
  • Gilks BC; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Grube M; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Harnett PR; Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
  • Harris HR; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Hartmann A; Institute of Pathology, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
  • Hein A; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
  • Hendley J; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia.
  • Hernandez BY; Institute of Pathology and Neuropathology, Tuebingen University Hospital, Tuebingen, Germany.
  • Heublein S; H12O-CNIO Lung Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Huang Y; Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
  • Huzarski T; Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Jakubowska A; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
  • Jimenez-Linan M; Department of Women's Health, Tuebingen University Hospital, Tuebingen, Germany.
  • Kennedy CJ; The University of Sydney, Sydney, NSW, Australia.
  • Kommoss FKF; Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW, Australia.
  • Koziak JM; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Kraemer B; Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Le ND; Institute of Pathology, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
  • Lesnock J; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
  • Lester J; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Br J Cancer ; 128(1): 137-147, 2023 01.
Article en En | MEDLINE | ID: mdl-36323878
ABSTRACT

BACKGROUND:

Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.

METHODS:

Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis.

RESULTS:

Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant.

CONCLUSION:

We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Cistadenocarcinoma Seroso Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: Br J Cancer Año: 2023 Tipo del documento: Article País de afiliación: Australia
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Cistadenocarcinoma Seroso Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: Br J Cancer Año: 2023 Tipo del documento: Article País de afiliación: Australia