Mutation of von Hippel-Lindau gene and expression of vascular endothelial growth factor in sporadic clear cell renal cell carcinoma and their relationships to angiogenesis

Abstract

To evaluate the relationship between the mutation of the von Hippel-Lindau (VHL) gene and expression of vascular endothelial growth factor (VEGF) in sporadic clear cell renal cell carcinoma (CCRCC) and angiogenesis. Polymerase chain reaction (PCR) was used to detect the mutation of VHL gene in the specimens of cancerous tissue and normal tissues away from tumor from 77 patients with CCRCC. Immunohistochemistry was used to examine the expression of VEGF. CD34 staining was used to measure the microvascular density (MVD). VHL gene mutations were detected in 40 cases (51.9%). The expression rate of VEGF was 79.2% (61 cases). The positive rate of VEGF in the cases with VHL mutation was 92.5%, significantly higher than that in the cases without VHL mutation (64.9%, P = 0.003). The levels of MVD was higher in the cases with VHL mutation and those with VEGF expression were 760.80/mm2 and 715.95/mm2 respectively, both significantly higher than those in the cases without VHL-mutation and those without VEGF expression (547.03/mm2 and 437.44/mm2 respectively, all P = 0.001). The cases with expression of VEGF were divided into two groups according the presence or absence of VHL gene mutations or not. The MVD of the cases with VEGF expression and VHL mutation was 760.80 mm2, significantly higher than that of the cases with VEGF expression and without VHL mutation (547.03 mm2, P = 0.011). The mutation rate of VHL gene is high among the Chinese with sporadic CCRCC. VHL gene mutation increases significantly the VEGF expression, thus, and perhaps via other mechanism too, promoting the angiogenesis in tumor. The high level of MVD of the cases with VHL gene mutation may be related to the high malignant potential of CCRCC.