Purpose: It has been found that expression of vascular endothelial growth factor‐C (VEGF‐C) in several carcinomas is significantly associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis. However, VEGF‐C expression in bladder transitional cell carcinoma (TCC) has not yet been reported. To elucidate the role of VEGF‐C in bladder TCC, we examined VEGF‐C expression in bladder TCC and pelvic lymph node metastasis specimens obtained from patients who underwent radical cystectomy.

Methods: Eighty‐seven patients who underwent radical cystectomy for clinically organ‐confined TCC of the bladder were enrolled in the present study. No neoadjuvant treatments, except transurethral resection of the tumor, were given to these patients. The VEGF‐C expressions of 87 bladder tumors and 20 pelvic lymph node metastasis specimens were examined immunohistochemically and the association between VEGF‐C expression and clinicopathological factors, including angiogenesis as evaluated by microvessel density (MVD), was also examined.

Results: Vascular endothelial growth factor‐C expression was found in the cytoplasm of tumor cells, but not in the normal transitional epithelium. Vascular endothelial growth factor‐C expression was significantly associated with the pathological T stage (P = 0.0289), pelvic lymph node metastasis (P < 0.0001), lymphatic involvement (P = 0.0008), venous involvement (P = 0.0002) and high MVD (P = 0.0043). The multivariate analysis demonstrated that VEGF‐C expression and high MVD in bladder TCC were independent risk factors influencing the pelvic lymph node metastasis. Moreover, the patients with VEGF‐C‐positive tumors had significantly poorer prognoses than those with the VEGF‐C‐negative tumors (P = 0.0087) in the univariate analysis. The multivariate analysis based on Cox proportional hazard model showed that the independent prognostic factors were patient age (P = 0.0132) and pelvic lymph node metastasis (P = 0.0333).

Conclusion: The present study suggests that VEGF‐C expression is an important predictive factor of pelvic lymph node metastasis in bladder cancer patients.