GLUT‐1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: Relationship to pimonidazole binding

Abstract

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.

Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer

“…Glucose transporter and ADM also showed significant correlation with each other. Glucose transporter 1 protein immunohistochemistry has previously been shown to correlate with CA IX staining in cervical cancer and, like CA IX, it has been shown to be a marker of tumour hypoxia (Airley et al, 2001(Airley et al, , 2003. The correlation here shows that the same is also likely to be true for bladder cancer.…”

Evaluation of hypoxia in an experimental rat tumour model by [18F]Fluoromisonidazole PET and immunohistochemistry

“…The extent of a positive correlation between immunohistochemical staining results for these markers is the subject of a controversial discussion. Although Olive et al (2001) found a very strong correlation (r ¼ 0.86, n ¼ 14) in human cervical cancer, Airley et al (2003) did not find a significant correlation (r ¼ 0.27; P ¼ 0.083, n ¼ 42). In head and neck cancer, Kaanders et al (2002) found a weak, but significant correlation (r ¼ 0.36; P ¼ 0.02, n ¼ 42).…”

“…To date, various methods are available to measure tumour oxygenation, including polarographic oxygen sensors (Vaupel et al, 1991), luminescence-based optical sensors (Bussink et al, 2000) and antibody-based detection of exogenous (Haustermans et al, 2000;Raleigh et al, 2001;Koch, 2002) and endogenous markers of hypoxia (Wykoff et al, 2000;Janssen et al, 2002;Airley et al, 2003). At this time, only the polarographic oxygen-sensor and the exogenous hypoxia marker pimonidazole (PIMO) can be considered as 'standard'.…”

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

“…Several studies have attempted to achieve this goal. Airley et al (2003) undertook a direct comparison of all three markers in cervix cancer specimens. The study concluded that there were similar staining patterns for all three markers and that they were significantly correlated with each other, although this comparison was made on a semiquantitative scoring system.…”

“…Of these, two proteins, carbonic anhydrase IX (CAIX) and glucose transporter-1 protein (GLUT1), have received much recent attention (Airley et al, 2001(Airley et al, , 2003Chia et al, 2001;Giatromanolaki et al, 2001;Loncaster et al, 2001;Olive et al, 2001;Swinson et al, 2003). In an initial series of bladder cancers, CAIX was found to colocalise with pimonidazole (Wykoff et al, 2000).…”