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The presence of hypoxia in tumours results in the overexpression of certain genes, which are controlled via the transcription factor HIF-1. Hypoxic cells are known to be radioresistant and chemoresistant, thus, a reliable surrogate marker of hypoxia is desirable to ensure that treatment may be rationally applied. Recently, the HIF-1-regulated proteins Glut-1 and CAIX were validated as intrinsic markers of hypoxia by comparison with pO(2) measured using oxygen electrodes. We compare the expression of Glut-1 and CAIX with the binding of the bioreductive drug hypoxia marker pimonidazole. Pimonidazole was administered to 42 patients with advanced carcinoma of the cervix, 16 hr before biopsy. Sections of single or multiple biopsies were then immunostained for Glut-1 and CAIX, and the area of staining scored by eye, using a "field-by-field" semi-quantitative averaging system. Using 1 biopsy only, Glut-1 (r = 0.54, p = <0.001) correlated with the level of pimonidazole binding, and Glut-1 and CAIX expression also correlated significantly (r = 0.40, p = <0.009). Thus, our study has shown that HIF-1 regulated genes have potential for future use as predictors of the malignant changes mediated by hypoxia, and warrant further investigation as indicators of response to cancer therapy.

Original publication




Journal article


Int J Cancer

Publication Date





85 - 91


Adult, Antigens, Neoplasm, Biomarkers, Biopsy, Carbonic Anhydrase IX, Carbonic Anhydrases, Carcinoma, Squamous Cell, Cell Hypoxia, DNA-Binding Proteins, Energy Metabolism, Female, Gene Expression Regulation, Neoplastic, Glucose Transporter Type 1, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Microelectrodes, Middle Aged, Monosaccharide Transport Proteins, Neoplasm Proteins, Nitroimidazoles, Nuclear Proteins, Observer Variation, Oxygen, Partial Pressure, Radiation-Sensitizing Agents, Reproducibility of Results, Transcription Factors, Uterine Cervical Neoplasms