Vascular Endothelial Growth Factor Is a Predictor of Relapse and Stage Progression in Superficial Bladder Cancer'

Tumor development is angiogenesis dependent, and vascular endothe 11*1 growth factor (VEGF) is a key growth factor in this process. We demonstrate that high expression of VEGF mRNA in 55 superficIal blad der cancers was associated with earlier recurrence (P = 0.001; hazard ratio, 3.09) and progression to a more invasive phenotype (P = 0.02; hazard ratio, 533). VEGF mRNA expression correlated with protein levels in superficial tumors (r 0.59, P 0.003) and normal bladder (r 0.65, P < 0.05), although the ratio of VEGF protein to mRNA was elevated In tumors compared to normal bladder (P = 0.004), suggesting posttranscriptional regulation. In this study, VEGF is implicated as a major downstream mediator of the effects of the p5.3 tumor suppressor gene by the association between high p53 protein (determined immuno chemically) and high VEGF protein and mRNA expression (P < 0.02), although in cases without high p53 protein expression, high VEGF mRNA also predicts a poor prognosis. The relationship between VEGF and early twnor recurrence suggests that seeding via angiogenesis may be a major mechanism in the pathogenesis of recurrence. These studies indicate that VEGF can predict the behavior of superfidal bladder tumors and is a therapeutic target for intravesical therapy.