Expression of hypoxia-inducible factor-1-alpha, hypoxia-inducible factor-2alpha and vascular endothelial growth factor in sporadic clear cell renal cell renal cell carcinoma and their significance in the pathogenesis thereof

Abstract

To investigate the expression of hypoxia-inducible factor (HIF)-1-alpha, HIF-2alpha, and vascular endothelial growth factor (VEGF) in sporadic clear cell renal cell carcinoma (CCRCC) and to analyze the relationship among them. Samples of CCRCC were obtained from 107 patients during resection. Immunohistochemistry was used to detect the expression of HIF-1-alpha, HIF-2alpha, and VEGF in the tumor tissues and normal kidney tissues distant from the tumor. The microvessel density (MVD) was observed by microscopy. HIF-1-alpha and HIF-2alpha were not expressed in the normal kidney tissues. However, in the tumor tissues the HIF-1-alpha positive rate was 69.2% (74/107), significantly lower than that of the HIF-2-alpha (80.5%, 88/107, P = 0.001), the VEGF positive rate was 78.5% (84/107). The VEGF positive rate of the HIF-1-alpha-positive group was 90.5%, significantly higher than that of the HIF-1-alpha-negative group (51.5%, P = 0.001). The VEGF positive rate of the HIF-2-alpha-positive group was 89.8%, significantly higher than that of the HIF-1-alpha-negative group (26.3%, P = 0.001). The MVD of the 64 HIF-1alpha, HIF-2alpha, and VEGF positive samples was 697, significantly higher than that of the 13 HIF-1alpha, HIF-2alpha, and VEGF negative samples (391, P = 0.001). The MVD of the HIF-2alpha positive samples was 678 +/- 324, significantly higher than that of the HIF-2alpha negative samples (383 +/- 293, P = 0.001). The MVD of the VEGF positive samples was 692 +/- 325, significantly higher than that of the VEGF negative samples (384 +/- 269, P = 0.001). Spearman correlation analysis showed that MVD was strongly positively correlated with HIF-2alpha and VEGF. Mann-Whitney U test showed that HIF-1alpha and HIF-2alpha were not correlated with the staging of CCRCC. HIF-2alpha is expressed more frequently in sporadic CCRCC than HIF-1alpha. Both HIF-1alpha and HIF-2alpha upregulate the VEGF expression and angiogenesis, especially HIF-2alpha.