Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Technology, Biology, Nuclear Science & Technology, Radiology, Nuclear Medicine & Medical Imaging, Life Sciences & Biomedicine - Other Topics, Colorectal cancer, hypoxia, intrinsic markers, CARBONIC-ANHYDRASE-IX, TUMOR HYPOXIA, IN-VITRO, EXPRESSION, CELLS, PIMONIDAZOLE, CARCINOMAS, ELECTRODES, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Cell Hypoxia, Colorectal Neoplasms, Female, Glucose Transporter Type 1, Humans, Hypoxia-Inducible Factor-Proline Dioxygenases, Male, Microvessels, Middle Aged, Monocarboxylic Acid Transporters, Nitroimidazoles, Procollagen-Proline Dioxygenase, Radiation-Sensitizing Agents, Survival Analysis, 06 Biological Sciences, 09 Engineering, 11 Medical and Health Sciences, Oncology & Carcinogenesis, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry

Abstract:

Abstract Objective: We evaluated the potential of some recently proposed hypoxia markers, being monocarboxylic acid transporter 1 (MCT1), MCT4 and prolyl hydroxylase 2 (PHD2); and a more established hypoxia marker, glucose transporter-1 (GLUT-1), by testing the association with the exogenous marker pimonidazole. Material/methods: Paraffin embedded tumour sections of 20 colorectal cancer patients were stained for blood vessels together with either pimonidazole or carbonic anhydrase-IX (CA-IX) and single stained for MCT1, MCT4, GLUT-1, and PHD2. Expression of all markers was compared with expression of pimonidazole and micro-vessel density (MVD) and with disease free survival (DFS) and overall survival (OS). Results: No correlation was found between the different intrinsic hypoxia markers tested and pimonidazole. A trend for high MCT1 expression in biopsies with low CA-IX expression was found (R=-0.45, p=0.06) and also the expression of MCT1 was higher in tumours with a high MVD (R=0.49, p=0.04). The more advanced tumours showed a higher expression of GLUT-1 (p=0.03). A low CA-IX expression in the tumour correlated with better DFS (p=0.03) and related to better OS (p=0.07). Conclusion: Although none of the tested intrinsic hypoxia markers correlated with pimonidazole staining, we confirmed the important role of both GLUT-1 and CA-IX for a more advanced pTNM (pathological tumour-node-metastasis) stage and DFS respectively.