Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

Abstract

To assess the relationship between protein and messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and subcellular localization of nuclear factor-kappa B (NF-kappaB), proliferation rate of tumor cells, and clinicopathological characteristics of renal cell tumors. We analyzed 31 one renal cell tumors - 22 clear cell renal cell carcinomas (CCRCC) and 9 other histologic types (non-CCRCC). VEGF expression and subcellular localization of p65 member of NF-kappaB and Ki67 were immunohistochemically evaluated for the proliferation rate of tumor cells. Expression of VEGF mRNA was assessed using quantitative real-time polymerase chain reaction after total RNA extraction from snap-frozen tumor tissue samples. Cytoplasmic localization of VEGF protein in renal cell tumors showed a perimembranous and diffuse pattern, the former being more evident in CCRCC (27.1 -/+ 18.9 vs 3.3 -/+ 10 % tumors, P<0.001) and the latter in non-CCRCC type (71.7 -/+ 23.2 vs 31.1 -/+ 22.1 % tumors, P<0.001). Heterogeneity in VEGF gene expression was more pronounced in CCRCC type than in non-CCRCC type (P=0.004). In addition, perimembranous VEGF pattern was associated with higher VEGF mRNA levels (P=0.006) and diffuse VEGF pattern with lower VEGF mRNA levels (P<0.001). Nuclear and cytoplasmic staining of NF-kappaB/p65 was observed in the majority of tumor cells. A significant association was recorded between cytoplasmic NK-kappaB/65 staining and VEGF staining of diffuse pattern (P=0.026). Association between NF-kappaB/65 and proliferation rate of tumor cells was significant for cytoplasmic staining (P=0.039) but not for nuclear NFkB/p65 staining (P=0.099). Higher but inhomogeneous expression of VEGF in tumor cells, especially in CCRCCs, is associated with NF-kappaB/65 activity. This indicates that both VEGF and NF-kappaB/65 may be important in renal carcinogenesis, representing a possible molecular target in the treatment of renal cell carcinoma.