title: Vascular endothelial growth factor-C (VEGF-C) expression predicts lymph node metastasis of transitional cell carcinoma of the bladder.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  The present study suggests that VEGF-C expression is an important predictive factor of pelvic lymph node metastasis in bladder cancer patients.
authors.affiliation: Department of Urology, Jichi Medical School, Tochigi, Japan. s.kazu@jichi.ac.jp
authors.forename: Kazumi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Morita
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tokue
mesh_terms: D000367:Age Factors; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015653:Cystectomy; D003593:Cytoplasm / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic; D010388:Pelvis; D011379:Prognosis; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D042582:Vascular Endothelial Growth Factor C