Non-endothelial KDR/flk-1 expression is associated with increased survival of patients with urothelial bladder carcinomas

AIMS: To investigate the immunohistochemical expression of KDR/flk-1 in a series of 114 urothelial bladder carcinomas in relation to clinicopathological parameters, Ki67, p53 and Bcl-2 protein expression and patient survival. KDR/flk-1 is a high-affinity tyrosine kinase receptor for vascular endothelial growth factor (VEGF), on vascular endothelium. However, there is increasing evidence that KDR/flk-1 is also expressed by normal non-endothelial and tumour cells. METHODS AND RESULTS: Immunohistochemistry was performed on paraffin sections using monoclonal and polyclonal antibodies. Statistical analysis was univariate (chi2 log rank test) and multivariate (Cox's model). KDR/flk-1 expression was observed in the cytoplasm of cancerous cells in 68.4% of cases. No statistically significant associations were observed between KDR/flk-1 expression and grade or stage of urothelial carcinomas, Ki67, p53 or Bcl-2 expression. In contrast, widespread KDR/flk-1 expression in more than 50% of cancerous cells was associated with increased survival, on univariate and multivariate analysis (P = 0.0119 and P = 0.042, respectively). CONCLUSIONS: Although the biological significance of non-endothelial KDR/flk-1 expression has not yet been elucidated, its association with better patient survival may be related to the failure of non-endothelial KDR/flk-1 to mediate angiogenic and mitogenic effects.