Levels of vascular endothelial growth factor (VEGF) in bladder cancer can predict the behaviour of T1G1 and T1G2 tumours
Crew JP., O'Bnen TS., Fuggle S., Bicknell R., Cranston DW., Harris AL.
Introduction: VEGF is an angiogenic factor elevated in superficial bladder cancer. We investigated the expression of VEGF in T1G1 and T1G2 bladder cancer to determine if it predicted tumour behaviour. The expression of the p53 tumour-suppressor gene, being a candidate gene for the control of VEGF, was also assessed to determine any correlation with VEGF expression in these tumours. Materials and methods: VEGF mRNA from 54 primary TIG1 or T1G2 bladder tumours was quantified using ribonuclease-protection analysis, protein was measured using an ELISA and p53 was expression assessed immunohistocheniically. The median follow-up was 24 months (range 6-48). Results: VEGF mRNA expression varied 300-fold between tumours and was correlated with protein levels (r = 0.61, P < 0.001). The median VEGF mRNA expression in tumours from 26 patients whose tumours recurred within 6 months wns three times higher than in the 28 whose tumours had not recurred (P = 0.003). Ten (37%) of the 27 tumours expressing levels of VEGF above the median progressed in stage compared with only two (7%) of those expressing levels below the median (P = 0.014). Positive staining for p53 was significantly associated with tumour recurrence (P = 0.002) and stage progression (P= 0.012) and was strongly associated with high VEGF expression (P < 0.001). A multivariate regression analysis confirmed that none of the other variables analysed (EGFR status, tumour grade, multiplicity, size, morphology, patient age, patient sex and smoking habit) significantly correlated with tumour behaviour in this study. Conclusion: VEGF is important in determining the behaviour of Tl bladder cancer and is able to predict recurrence and progression in these patients. The p53 gene may be involved in the control of VEGF expression. © 1997 British Journal of Urology.