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

HIF-1 alpha induces GLUT-1 expression, and their presence has been evaluated in colorectal cancer. However, the expressions of GLUT-1 and HIF-1a 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-1 alpha and GLUT-1 with various clinicopathological features of colorectal cancer. The presence of HIF-1 alpha 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-1 alpha 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 HIF1 alpha with significantly greater frequency than mucinous adenocarcinomas (p=0.002, p=0.0002, respectively). GLUT-1 and HIF-1 alpha 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-1 alpha correlated with grade (p=0.00003) without difference with regard to pN status. HIF-1 alpha 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-1cc and GLUT-1 does not directly prove the dependence between HIF-1 alpha as a nuclear transcriptional factor and GLUT-1 as its downstream protein, it is evidence of their simultaneous upregulation. The extranuclear accumulation of HIF-1 alpha and GLUT-1 requires further studies to explain its significance in colorectal cancer.