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Clinicopathological significance and linkage of the distribution of HIF-1α and GLUT-1 in human primary colorectal cancer

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Pathology & Oncology Research

Abstract

HIF-la induces GLUT-1 expression, and their presence has been evaluated in colorectal cancer. However, the expressions of GLUT-1 and HIF-lα 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-lα and GLUT-1 with various clinicopathological features of colorectal cancer. The presence of HIF-lα 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-la 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-lα with significantly greater frequency than mucinous adenocarcinomas (p=0.002, p=0.0002, respectively). GLUT-1 and HIF-la 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-lα correlated with grade (p=0.00003) without difference with regard to pN status. HIF-lα expression correlated with GLUT-1 expression in the whole patient population, as well as in all clinicopathological groups except for the pTl+pT2 group. Although the coexpression of cytoplasmic HIF-la 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-la and GLUT-1 requires further studies to explain its significance in colorectal cancer.

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Correspondence to Stanislaw Sulkowski PhD.

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Wincewicz, A., Sulkowska, M., Koda, M. et al. Clinicopathological significance and linkage of the distribution of HIF-1α and GLUT-1 in human primary colorectal cancer. Pathol. Oncol. Res. 13, 15–20 (2007). https://doi.org/10.1007/BF02893436

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