title: Expression of vascular endothelial growth factor in patients with testicular germ cell tumors as an indicator of metastatic disease.
abstract: BACKGROUND
  Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor (PD-ECGF) are involved in increased angiogenic activity and disease progression in solid tumors. However, there is no information regarding the association of these angiogenic factors with clinicopathologic findings in testicular germ cell tumors (GCTs).
  
  
  METHODS
  The authors examined the expression of VEGF and TP as well as microvessel density in GCTs and their association with clinicopathologic findings. Expression of VEGF and TP and microvessel density were examined immunohistochemically in 80 GCTs, including 33 seminomas (25 tumors with organ-confined disease and 8 with metastasis) and 47 nonseminomatous testicular GCTs (NSGCTs) (20 tumors with organ-confined disease and 27 with metastasis). Expression of VEGF also was examined in four GCTs and one nonneoplastic testis by immunoblotting.
  
  
  RESULTS
  VEGF protein was expressed more highly in GCTs compared with nonneoplastic testes. VEGF expression in GCTs was correlated significantly with microvessel count (P < 0.001). Both VEGF expression and microvessel count were correlated with metastasis in seminoma (P = 0.008 and P < 0.001, respectively), but only VEGF expression was identified as statistically significant by multiple regression analysis (P = 0.006). Conversely, four variables (VEGF expression, microvessel count, the presence of venous invasion, and the presence of embryonal carcinoma elements in the primary tumor) were correlated with metastasis in NSGCT (P < 0.001, P < 0.001, P = 0.004, and P = 0.029, respectively). However, multiple regression analysis revealed that only VEGF expression and microvessel count were significant factors for metastasis (P < 0.007 and P < 0.001, respectively). In contrast, high levels of TP were observed in infiltrating cells, but not in the majority of cancer cells.
  
  
  CONCLUSIONS
  The findings of the current study suggest that VEGF expression is involved in tumor development, angiogenesis, and metastasis in GCT.
authors: Department of Urology, Faculty of Medicine, Kagoshima University, Japan.
authors: S
authors: S
authors: Fukuda
authors: T
authors: T
authors: Shirahama
authors: Y
authors: Y
authors: Imazono
authors: T
authors: T
authors: Tsushima
authors: H
authors: H
authors: Ohmori
authors: T
authors: T
authors: Kayajima
authors: S
authors: S
authors: Take
authors: K
authors: K
authors: Nishiyama
authors: S
authors: S
authors: Yonezawa
authors: S
authors: S
authors: Akiba
authors: S
authors: S
authors: Akiyama
authors: Y
authors: Y
authors: Ohi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D016228:Endothelial Growth Factors / Q000032:analysis*; D018237:Germinoma / Q000098:blood supply / Q000737:chemistry* / Q000175:diagnosis / Q000556:secondary*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007223:Infant; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013736:Testicular Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D013737:Testis / Q000737:chemistry; D013939:Thymidine Phosphorylase / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013939:Thymidine Phosphorylase