201. Clinicopathological significance and linkage of the distribution of HIF-1alpha and GLUT-1 in human primary colorectal cancer.
- Author
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Wincewicz A, Sulkowska M, Koda M, and Sulkowski S
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma, Mucinous pathology, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Colorectal Neoplasms pathology, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Staging, Adenocarcinoma metabolism, Adenocarcinoma, Mucinous metabolism, Colorectal Neoplasms metabolism, Glucose Transporter Type 1 metabolism, Hypoxia-Inducible Factor 1, alpha Subunit metabolism
- Abstract
HIF-1alpha induces GLUT-1 expression, and their presence has been evaluated in colorectal cancer. However, the expressions of GLUT-1 and HIF-1alpha have not been investigated together with reference to clinicopathological characteristics in human colorectal cancer. The aim of our study was to compare the expression of HIF-1alpha and GLUT-1 with various clinicopathological features of colorectal cancer. The presence of HIF-1alpha and GLUT-1 was visualized immunohistochemically in 123 primary tumors. Membranous localization of GLUT-1 was found in multifocally necrotizing cancer samples, while pure cytoplasmic perinuclear, mostly supranuclear GLUT-1 accumulation was characteristic of cancer fields with lack of necrosis. HIF-1alpha was located in the cytoplasm and occasionally in the nuclei of cancer cells. Immunoreactivity to GLUT-1 was significantly higher in node-positive cancers compared with nodenegative ones (p=0.04), confirming our earlier results obtained on a larger number of patients. Non-mucinous adenocarcinomas expressed GLUT-1 and HIF-1alpha with significantly greater frequency than mucinous adenocarcinomas (p=0.002, p=0.0002, respectively). GLUT-1 and HIF-1alpha expression did not differ in relation to tumor stage, location, or patients' age or gender. In contrast to that of GLUT-1, expression of HIF-1alpha correlated with grade (p=0.00003) without difference with regard to pN status. HIF-1alpha expression correlated with GLUT-1 expression in the whole patient population, as well as in all clinicopathological groups except for the pT1+pT2 group. Although the coexpression of cytoplasmic HIF-1alpha and GLUT-1 does not directly prove the dependence between HIF-1 as a nuclear transcriptional factor and GLUT-1 as its downstream protein, it is evidence of their simultaneous upregulation. The extranuclear accumulation of HIF-1alpha and GLUT-1 requires further studies to explain its significance in colorectal cancer.
- Published
- 2007
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