[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

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.