Expression of vascular endothelial growth factor gene and its receptor (flt-1) gene in urinary bladder cancer.

We investigated expression of the vascular endothelial growth factor (VEGF) gene and its receptor gene (flt-1) in 30 patients with transitional cell carcinoma (TCC) of the urinary bladder by Northern blot hybridization analysis. The VEGF transcript was observed in all of the tumors and the normal mucosae. Of the 20 tumors in which a comparative study was done, eight (40.0%) overexpressed the gene with a tumor versus normal ratio of equal to and greater than 3.0. Invasive TCCs expressed significantly more VEGF gene than superficial TCCs. Cytoplasm of tumor cells was positively stained by immunohistochemistry with an anti-VEGF monoclonal antibody, while the intratumoral endothelial cells and the vascular smooth muscle cells were weakly positive for the staining. TCCs, normal mucosae and human umbilical endothelial cells expressed flt-1 gene, while leucocytes from peripheral blood did not. The expression level of flt-1 gene significantly correlated with that of the VEGF gene in the tumor. These results indicate that the VEGF gene is frequently overexpressed in TCC of the urinary bladder, especially in muscle invasive tumors, and that a paracrine system including VEGF and flt-1 exists between the TCC cells and the adjacent endothelial cells so as to regulate the angiogenesis in this tumor.