Expression of hypoxia-inducible factor-1α predicts benefit from hypoxia modification in invasive bladder cancer

• Published in: British journal of cancer Vol. 111; no. 3; pp. 437 - 443
• Main Authors: Hunter, B A, Eustace, A, Irlam, J J, Valentine, H R, Denley, H, Oguejiofor, K K, Swindell, R, Hoskin, P J, Choudhury, A, West, C M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29-07-2014; Nature Publishing Group
• Subjects: 692/53/2423; 692/699/67/589/1336; Aged; Biological and medical sciences; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Transitional Cell - metabolism; Carcinoma, Transitional Cell - mortality; Carcinoma, Transitional Cell - therapy; Cell Hypoxia; Chemoradiotherapy; Clinical Study; Disease-Free Survival; Drug Resistance; Epidemiology; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Kaplan-Meier Estimate; Male; Medical sciences; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Invasiveness; Nephrology. Urinary tract diseases; Oncology; Proportional Hazards Models; Retrospective Studies; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - therapy; Urinary tract. Prostate gland; hypoxia; HIF-1; GLUT1; CAIX; biomarkers; bladder; BCON; Modification; Oxygen; Urinary system disease; Prediction; Biological marker; HIF-1α; Urinary tract disease; Malignant tumor; Bladder cancer; Cancerology; Urinary system; Urinary bladder; GLUT1 glucose transporter; Hypoxia; Bladder disease; Transcription factor HIF1; Invasive cancer; Predictive factor; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.315

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-1
α
(HIF-1
α
) 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-1
α
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-1
α
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-1
α
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-1
α
may be used to predict benefit from CON in patients with bladder cancer but does not improve on use of necrosis.