The expression and distribution of vascular endothelial growth factor in bladder cancer
Crew JP., Turley H., Fuggle S., Cranston DW., Harris AL.
Introduction: Vascular endothelial growth factor (VEGF) is a principal factor in tumour angiogenesis. We have previously shown that the expression of VEGF within either the tumour or urine of patients with bladder cancer is related to prognosis. This study examines the distribution of VEGF mRNA and protein in bladder cancer using in sit hybridization (ISH) and immunohistochemistry (IHC). Materials and methods: Paraffin sections from 32 primary bladder cancers (3 Ta, 1 5 T1 and 11 ≥ T2) and three specimens of normal bladder were immunostained using a monoclonal antibody against all VEGF isoforms. A 35S-labelled RNA riboprobe against the VEGF 121aa isoform was used for the ISH. Results: VEGF protein and mRNA were detectable in all sections. Bladder cancers were more strongly positive for both VEGF mRNA and protein than were normal urothelium, with maximal immunopositivity within the tumour cell cytoplasm. VEGF expression was stronger in stage ≥ Tl tumours than in Ta but varied markedly between different tumours and between different areas within the same tumour. T1 tumours formed a highly heterogeneous group, with tumours having a poor prognosis staining most strongly. Tumour cells adjacent to the bladder lumen, areas of necrosis, inflammation or carcinoma in situ (CIS) had enhanced expression of both VEGF mRNA and protein. Conclusion: There was marked expression of VEGF within bladder cancer cells. Heterogeneity of expression between tumours and the association with a poor prognosis in Tl tumours indicates that VEGF IHC may have prognostic capability. High expression in areas of CIS could account for the poor prognosis associated with this pathology. Enhanced expression within tumour cells adjacent to the bladder lumen may account for the high urinary VEGF levels in patients with bladder cancer and supports the importance of angiogenesis in the pathogenesis of tumour cell implantation and tumour recurrence, highlighting the value of anti-VEGF therapeutic strategies against tumour recurrence. © 1998 British Journal of Urology.