title: Profiling of VEGFs and VEGFRs as prognostic factors in soft tissue sarcoma: VEGFR-3 is an independent predictor of poor prognosis.
abstract: BACKGROUND
  In non-gastrointestinal stromal tumor soft tissue sarcoma (non-GIST STS) optimal treatment is surgery with wide resection margins. Vascular endothelial growth factors (VEGFs) and receptors (VEGFRs) are known to be key players in the initiation of angiogenesis and lymphangiogenesis. This study investigates the prognostic impact of VEGFs and VEGFRs in non-GIST STS with wide and non-wide resection margins.
  
  
  METHODS
  Tumor samples from 249 patients with non-GIST STS were obtained and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expressions of VEGF-A, -C and -D and VEGFR-1, -2 and -3.
  
  
  RESULTS
  In the univariate analyses, VEGF-A (P=0.040) in the total material, and VEGF-A (P=0.018), VEGF-C (P=0.025) and VEGFR-3 (P=0.027) in the subgroup with wide resection margins, were significant negative prognostic indicators of disease-specific survival (DSS). In the multivariate analysis, high expression of VEGFR-3 (P=0.042, HR=1.907, 95% CI 1.024-3.549) was an independent significant negative prognostic marker for DSS among patients with wide resection margins.
  
  
  CONCLUSIONS
  VEGFR-3 is a strong and independent negative prognostic marker for non-GIST STSs with wide resection margins.
authors.affiliation: Institute of Medical Biology, University of Tromso, and Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Kilvaer
authors.forename: Andrej
authors.initials: A
authors.lastname: Valkov
authors.forename: Sveinung
authors.initials: S
authors.lastname: Sorbye
authors.forename: Eivind
authors.initials: E
authors.lastname: Smeland
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D042583:Lymphangiogenesis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism* / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000401:mortality; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D040321:Vascular Endothelial Growth Factor Receptor-3