title: Hypoxia Marker GLUT-1 (Glucose Transporter 1) is an Independent Prognostic Factor for Survival in Bladder Cancer Patients Treated with Radical Cystectomy.
abstract: BACKGROUND
  Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy.
  
  
  METHODS
  279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1-α, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors.
  
  
  RESULTS
  In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95% CI 0.7-12.6, Waldp= 0.15 in the Toronto cohort and HR 3.2, 95% CI 1.3-7.5, Waldp= 0.0085 in the Turku cohort).
  
  
  CONCLUSIONS
  GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours.
authors.affiliation: Department of Surgical Oncology, University of Toronto and Princess Margaret Hospital (University Health Network), Toronto, ON, Canada; Department of Urology, Turku University Hospital, Turku, Finland.
authors.forename: P J
authors.initials: PJ
authors.lastname: Boström
authors.affiliation: Department of Radiation Oncology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Thoms
authors.affiliation: Department of Biostatistics, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Sykes
authors.affiliation: Department of Radiation Oncology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: O
authors.initials: O
authors.lastname: Ahmed
authors.affiliation: Department of Pathology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Evans
authors.affiliation: Department of Surgical Oncology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: B W G
authors.initials: BW
authors.lastname: van Rhijn
authors.affiliation: Department of Pathology, Helsinki University Hospital, Helsinki, Finland; Institute for Molecular Medicine (FIMM), Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Mirtti
authors.affiliation: Department of Surgical Oncology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: O
authors.initials: O
authors.lastname: Stakhovskyi
authors.affiliation: Department of Urology, Turku University Hospital , Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Laato
authors.affiliation: Department of Surgical Oncology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Margel
authors.affiliation: Department of Biostatistics, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Pintilie
authors.affiliation: Department of Surgical Oncology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Kuk
authors.affiliation: Department of Radiation Oncology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Milosevic
authors.affiliation: Department of Surgical Oncology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: A R
authors.initials: AR
authors.lastname: Zlotta
authors.affiliation: Department of Radiation Oncology, University of Toronto and Princess Margaret Hospital (University Health Network) , Toronto, ON, Canada.
authors.forename: R G
authors.initials: RG
authors.lastname: Bristow
keywords: Bladder cancer; CAIX; GLUT-1; HIF1α; hypoxia