Expression of Vascular Endothelial Growth Factor, Receptor KDR and p53 Protein in Transitional Cell Carcinoma of the Bladder

Abstract

Aim: To evaluate the expression profile of vascular endothelial growth factor (VEGF), kinase-insert-domain-containing receptor (KDR) and p53 in patients from Northeastern China with transitional cell carcinoma (TCC) of bladder. Materials and Methods: One hundred and twelve patients with bladder transitional cell carcinoma were involved in this study. The expression of VEGF, KDR and p53 were evaluated by immunohistochemical staining on paraffin-embedded slides. The correlations between the biomarkers with clinical pathological characteristics were assessed; the co-expression of VEGF and KDR in tumor cells as well as the correlation between p53 and VEGF/KDR expression were analyzed. Results: Expression of VEGF, KDR and p53 was observed in 69.6, 55.4 and 48.2% of TCC patients, respectively. VEGF, KDR and p53 expressions were found to be higher in the invasive bladder tumors than in the superficial tumors, and KDR and p53 expression were significantly associated with higher tumor grade. Co-expression of VEGF and KDR was found in 51 patients, and VEGF expression was associated with KDR expression. Positive correlations were found between p53 protein and VEGF/KDR expression. Conclusion: Our results suggest that VEGF, KDR and p53 might be valuable biomarkers in prognosis of TCC patients. Co-expression of VEGF and KDR implied an autocrine signaling of VEGF in tumor cells, and the results of immunohistochemical staining supported the role of p53 gene in the process of angiogenesis.

Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C

“…In conclusion, a number of studies indicate that VEGF concentrations are prognostic for outcomes in bladder cancer [7,9–13,28]. Furthermore, clinical and pre‐clinical studies have indicated that adding anti‐VEGF therapies to TCC chemotherapy leads to improved treatment effectiveness, and clinical trials are under way to test these outcomes [37,38].…”

“…Increased expression of VEGFR‐2 in TCC correlates with disease stage and increases with tumour invasion into the muscle [7,28]. VEGFR‐1 also is expressed in T‐24 cells [7] and in bladder cancer [26,28]. Therefore, we examined the effect of MMC on concentrations of VEGFR‐2 (KDR/flk‐1) and VEGFR‐1 (Flt‐1) Treatment with MMC did not change VEGFR‐1 mRNA in T‐24 cells.…”

“…Increased expression of VEGFR-2 in TCC correlates with disease stage and increases with tumour invasion into the muscle [7,28]. VEGFR-1 also is expressed in T-24 cells [7] and in bladder cancer [26,28]. Therefore, we examined the effect of MMC on concentrations of VEGFR-2 (KDR/flk-1) and The up-regulation of VEGFR-2 protein and mRNA induced by MMC in bladder cancer cells and the recent observation by Saban et al [29,30] that urothelial VEGF receptors are up-regulated by inflammation, including acute and chronic inflammation induced by BCG, led us to speculate on whether MMC increased VEGFR-2 in normal urothelial tissue.…”

“…In conclusion, a number of studies indicate that VEGF concentrations are prognostic for outcomes in bladder cancer [7,[9][10][11][12][13]28].…”

SLT-VEGF Reduces Lung Metastases, Decreases Tumor Recurrence, and Improves Survival in an Orthotopic Melanoma Model

“…Considering that tumor cells may express VEGF receptors [19,20,21], and that even non-receptor mediated SLT-VEGF toxicity might be cell-specific, we explored the sensitivity of Line IV Cl 1 melanoma cells to SLT-VEGF in vitro . We found that these cells are essentially negative for VEGFR-2 expression (Figure 1A) and their growth is inhibited by SLT-VEGF at a 100-fold higher IC 50 of 70 nM (Figure 1B).…”