Glucose transporter-1
protein (GLUT1) and
carbonic anhydrase IX (CAIX) are regulated by
hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for
hypoxia. This study directly compares CAIX and GLUT1 with
pimonidazole binding in a prospective series of
bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of
bladder cancer patients treated in a phase II trial of radical
radiotherapy with
carbogen and
nicotinamide (ARCON). A total of 21 patients with a diagnosis of
transitional cell carcinoma of the bladder received 0.5 g m(-2)
pimonidazole. Serial tumour sections were stained for
pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive
bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with
pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P=0.0001) for GLUT1 and 0.74 (P<0.0001) for CAIX. In both series of patients, the intrinsic
hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The
hypoxia markers did not predict for local control or
metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both
hypoxia modification and accelerated treatment may be valid treatment options in
bladder cancer.