Tumor development is angiogenesis dependent, and vascular endothelial growth factor (VEGF) is a key growth factor in this process. We demonstrate that high expression of VEGF mRNA in 55 superficial bladder 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, 5.33). 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 p53 tumor suppressor gene by the association between high p53 protein (determined immunochemically) 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 tumor 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 superficial bladder tumors and is a therapeutic target for intravesical therapy.
J. P. C. was supported by the Lillian May Coleman Research Scholarship of the Royal College of Surgeons of England. T. O. was supported by the Private Patients Plan Scholarship of the Royal College of Surgeons of England. S. F. was supported by the Medical Research Council. M. B., R. B., and A. L. H. are supported by the Imperial Cancer Research Fund.