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

作者：JEREMY P. CREW, Tim O’Brien, Mike J Bradburn, S Fuggle, Roy Bicknell, David Cranston, Adrian L. Harris · 发表于：The Journal of Urology · 年份：1998 · DOI：10.1097/00005392-199811000-00090 · 被引用次数：227 · 研究领域：Bladder and Urothelial Cancer Treatments、Cancer, Hypoxia, and Metabolism、Cancer, Lipids, and Metabolism

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.