Brain-Specific Angiogenesis Inhibitor 1 is a Putative Factor for Inhibition of Neovascular Formation in Renal Cell Carcinoma

Purpose: Renal cell carcinoma is a typical hypervascular tumor in which neovascularization may have a large part in progression. We examined expression of the cancer regulating, p53 targeted angiogenesis inhibitor brain-specific angiogenesis inhibitor 1 in renal cell carcinoma tissue to elucidate the clinical significance of its expression. Materials and Methods: We examined brain-specific angiogenesis inhibitor 1 mRNA and protein expression in 47 renal cell carcinoma and 10 normal kidney tissues using real-time quantitative polymerase chain reaction and immunohistochemistry, respectively. Levels of VEGF and bFGF mRNA, and immunohistochemical expression of p53 protein were also investigated in the same renal cell carcinoma tissues. Results: A significant decrease in BAI1 mRNA was noted in renal cell carcinoma tissue compared with that in normal kidney tissue (p < 0.001). Immunostaining for brain-specific angiogenesis inhibitor 1 was also decreased in carcinoma tissue compared with normal kidney tissue. BAI1 mRNA and protein expression were lower in advanced renal cell carcinoma (pT3-4) than in localized renal cell carcinoma (pT1-2) tissues (p < 0.03 and 0.003, respectively). A significant negative correlation was observed between microvessel density and brain-specific angiogenesis inhibitor 1 protein expression (r = -0.4056, p = 0.002). No significant correlation was noted between BAI1 and VEGF or bFGF mRNA levels. Brain-specific angiogenesis inhibitor 1 protein expression did not correlate with p53 protein expression. Conclusions: These observations suggest that down-regulation of brain-specific angiogenesis inhibitor 1 expression may be a critical factor in renal cell carcinoma development and BAI1 may be a promising candidate for gene therapy of renal cell carcinoma.