Vascular endothelial growth factor: A role in bladder cancer recurrence and stage progression?

Introduction: The 'clonal origin' hypothesis of bladder cancer states that cells from a primary tumour may be shed and implant to give rise to a recurrence. Angiogenesis is necessary for tumour development and tumour cells expressing high levels of angiogenic factors may have a survival advantage because they are able to stimulate vessel growth, facilitating implantation. As vascular endothelial growth factor (VEGF) is central to tumour angiogenesis. this hypothesis was tested by determining if VEGF mRNA and protein increased in recurrent bladder tumours. Materials and methods: Total RNA and protein was prepared from 24 primary bladder cancers and their recurrences. VEGF mRNA and protein were quantified using ribonuclease protection assay and an ELISA (respectively). Results: In 15 bladder tumours (eight pT1. seven > T2) that recurred without stage progression there was no significant change in either VEGF mRNA or protein (P > 0.01) between the primaries and recurrences. In two patients with tumours that recurred frequently. VEGF protein increased over fivefold in the first recurrence. In nine patients the superficial (pT1) primary tumour recurred and progressed to muscle invasion. This stage progression was accompanied by a switch in expression of VEGF to one resembling that of a primary muscle-invasive tumour with a reduction in VEGF mRNA (P = 0.02) accompanying an increase in VEGF protein expression (P = 0.04). Conclusion: VEGF does not increase in all recurrent tumours, but increased VEGF proteins in stage-progressive and frequently recurring tumours supports an involvement in recurrence and progression. The switch in VEGF expression observed in superficial bladder cancers that undergo stage progression suggests an alteration in molecular biology that may represent the induction of factors regulating translation which could offer targets for new treatment strategies. © 1998 British Journal of Urology.