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

Hoskin, PJ; Sibtain, A; Daley, FM; Wilson, GD; (2003) GLUTI and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON. British Journal of Cancer , 89 (7) pp. 1290-1297. 10.1038/sj.bjc.6601260.

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Abstract

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

Type: Article
Title: GLUTI and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON
DOI: 10.1038/sj.bjc.6601260
Additional information: Journal English Article NATURE PUBLISHING GROUP 0 OCT 6 729XC LONDON Hoskin PJ Mt Vernon Canc Ctr, CR UK Tumour Biol & Radiat Therapy Grp, Rickmansworth Rd, Northwood HA6 2RN, Middx, England BRIT J CANCER MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Keywords: Agreement, As, BINDING, bladder, bladder cancer, cancer, CANCER PATIENTS, CANCER-PATIENTS, carbonic anhydrase IX, CARBONIC-ANHYDRASE-IX, Carcinoma, cell, CELL-CARCINOMA, Cellular, COEFFICIENTS, colocalisation, COMBINATION, control, Correlation, diagnosis, English, FAILURE, Glucose, glucose transporter protein 1 (GLUT1), GLUCOSE-TRANSPORTER, hypoxia, Indices, intrinsic, local, Local Control, LOCAL-CONTROL, MARKER, Markers, May, nature, Other, outcome, OXYGEN MEASUREMENTS, Patient, patients, phase, PHASE II, pimonidazole, PIMONIDAZOLE BINDING, POOR SURVIVAL, PREDICTORS, prognostic, PROGNOSTIC-SIGNIFICANCE, proliferation, PROTEIN, Publishing, Radiotherapy, RD, relationship, Retrospective Studies, SERIES, ST, SURVIVAL, therapy, Tissue, together, TRANSITIONAL-CELL CARCINOMA, treatment, TREATMENT TIME, TRIAL, TUMOR HYPOXIA, Tumour, UK, VASCULARITY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/6878
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