Vascular Endothelial Growth Factor and Thrombospondin-1 mRNA Expression in Bladder Tumors: Correlation with Histopathology and Prognosis

Abstract

Objective: The purpose of this study was to determine genetic expression levels of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) in fresh bladder tumor specimens and evaluate their relationship with tumor histopathological features and their prognostic value in recurrence and progression in patients with bladder cancer. Materials and Methods: Patients who were treated for urothelial cancer of the bladder and followed for at least 6 months were included in this retrospective study. Following RNA isolation from fresh tumor tissue samples recovered from transurethral resection or radical cystectomy specimens, VEGF and TSP-1 mRNA expression was analysed by reverse transcription polymerase chain reaction (RT-PCR). The findings were examined in relation to the histopathological parameters and recurrence and progression rates of the respective tumors. Results: Sixty-eight patients were included in the study. Mean follow-up time was 22.6 months. In patients with non-muscle-invasive urothelial bladder cancer (NMIBC), rates of recurrence and progression were 64\% and 35\%, respectively. RT-PCR analyses revealed VEGF mRNA expression in 29 patients (43\%) and TSP-1 mRNA expression in 22 patients (32\%). Recurrence and progression were observed during follow-up in 64\% and 24\% of the 25 NIMBC patients with positive VEGF expression, while these rates were 63\% and 30\% among the 30 NIMBC patients with no VEGF expression, respectively. Rates of recurrence and progression during follow-up were 70\% and 30\% among NIMBC patients with positive TSP-1 expression and 60\% and 26\% among patients with no TSP-1 mRNA expression, respectively. Conclusion: In this study, VEGF and TSP-1 mRNA expression was not associated with histological grade or stage of bladder cancer. There was no difference in VEGF expression in tumor tissues from NIMBC patients with or without disease recurrence. Though lacking statistical significance, a positive correlation between TSP-1 expression and tumor recurrence and progression was seen among the NIMBC patients in our study. Although stimulatory and inhibitory factors are known to regulate angiogenesis, no definitive conclusions have been reached regarding their mechanism of action or the prognostic significance of their up-or down-regulation.