Vascular Endothelial Growth Inhibitor 174 Is a Negative Regulator of Aggressiveness and Microvascular Density in Human Clear Cell Renal Cell Carcinoma

Aims: To evaluate the role and expression of vascular endothelial growth inhibitor isoform 174 (VEGI 174) in the microvessels and its correlation with microvessel density (MVD) and prognosis of clear cell renal cell carcinoma (CCRCC). Materials and Methods: Immunohistochemical analysis was performed in 98 cases of renal cell carcinoma and paired normal kidney tissues for VEGI 174 and CD34. The clinical, pathological and follow-up (median follow-up: 54.5 months) information were recorded and analyzed against the VEGI174 and MVD expression. Results: There was an inverse correlation between VEGI 174 and MVD (r=-0.420, p<0.05) in normal human renal tissues and CCRCC specimens. Compared to normal kidney tissues, the expression of VEGI 174 was significantly lower in CCRCC (0.420 +/- 0.151 vs 0.107 +/- 0.063, p<0.01, respectively). On the contrary, MVD was higher in CCRCC specimens than in normal renal tissues (72.020 +/- 31.709 vs. 53.480 +/- 11.071, p<0.01, respectively). The expression of VEGI 174 in G1+G2 tumors was significantly higher than in G3 tumors (0.132 +/- 0.055 vs. 0.044 +/- 0.025, p<0.05, respectively). There was also a statistical significance in the expression of VEGI 174 in patients of different ages (<60y, 0.102 +/- 0.054 vs. >= 60 years, 0.117 +/- 9.083, p<0.01, respectively). However, between the staining of VEGI 174 and other pathological parameters (gender, tumour size and stage), there were no significant statistical differences (p>0.05). In addition, MVDs did not differ statistically by pathological grade, stage, gender, age or tumor size (p>0.05). Four patients died of CCRCC-related conditions during follow-up. However, no relationship between the expression of VEGI 174/MVD and overall survival was found in the study (p>0.05). Conclusion: VEGI 174 has a significant role in angiogenesis in CCRCC, and appears to be a negative regulator of aggressiveness during the development and progression of CCRCC.