Expression of hypoxia-inducible factor-1α predicts benefit from hypoxia modification in invasive bladder cancer.
Hunter, Benjamin A Eustace, A Irlam, Joely J Valentine, Helen R Denley, H Oguejiofor, Kenneth K Swindell, Ric Hoskin, P Choudhury, Ananya West, Catharine M L
Hunter, Benjamin A
Eustace, A
Irlam, Joely J
Valentine, Helen R
Denley, H
Oguejiofor, Kenneth K
Swindell, Ric
Hoskin, P
Choudhury, Ananya
West, Catharine M L
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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.British Journal of Cancer advance online publication, 17 June 2014; doi:10.1038/bjc.2014.315 www.bjcancer.com.
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2014-06-17
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Expression of hypoxia-inducible factor-1α predicts benefit from hypoxia modification in invasive bladder cancer. 2014: Br J Cancer