title: Expression of hypoxia-inducible factor-1α predicts benefit from hypoxia modification in invasive bladder cancer.
abstract: BACKGROUND
  The addition of carbogen and nicotinamide (CON) to radiotherapy (RT) improves overall survival in invasive bladder cancer. We explored whether expression of the hypoxia marker hypoxia-inducible factor-1α (HIF-1α) alone or in combination with other markers predicted benefit from CON.
  
  
  METHODS
  A retrospective study was carried out using material from patients with high-grade invasive bladder carcinoma enrolled in the BCON phase III trial of RT alone or with CON (RT+CON). HIF-1α expression was studied in 137 tumours using tissue microarrays and immunohistochemistry. Data were available from other studies for carbonic anhydrase IX and glucose transporter 1 protein and gene expression and tumour necrosis.
  
  
  RESULTS
  Patients with high HIF-1α expression had improved 5-year local relapse-free survival with RT+CON (47%) compared with RT alone (21%; hazard ratio (HR) 0.48, 95% CI 0.26-0.8, P=0.02), no benefit was seen with low HIF-1α expression (HR 0.81, 95% CI 0.43-1.50, P=0.5). Combinations of markers including necrosis also predicted benefit but did not improve on prediction using necrosis alone.
  
  
  CONCLUSIONS
  HIF-1α may be used to predict benefit from CON in patients with bladder cancer but does not improve on use of necrosis.
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: B A
authors.initials: BA
authors.lastname: Hunter
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Eustace
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: J J
authors.initials: JJ
authors.lastname: Irlam
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: H R
authors.initials: HR
authors.lastname: Valentine
authors.affiliation: Department of Histopathology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
authors.forename: H
authors.initials: H
authors.lastname: Denley
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: K K
authors.initials: KK
authors.lastname: Oguejiofor
authors.affiliation: Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK.
authors.forename: R
authors.initials: R
authors.lastname: Swindell
authors.affiliation: Cancer Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hoskin
authors.affiliation: Department of Clinical Oncology, University of Manchester, Manchester Academic Health Centre, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Choudhury
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: West
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D015687:Cell Hypoxia; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit