title: Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer: a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  The aim of this study was to explore the co-expression and prognostic relevance of thrombospondin-1 (THBS-1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR-1) in epithelial ovarian cancer (EOC).
  
  
  METHODS
  Frozen tumor specimens with defined p53 status were obtained from 67 patients with previously untreated advanced-stage EOC who participated in a Gynecologic Oncology Group specimen-banking protocol and a phase III treatment protocol. Relative expression of the angiogenic markers was quantified by immunoblot analysis and categorized at the median angiogenic marker/actin ratio. p-values are provided as an indication of confidence in the results and to prioritize further testing.
  
  
  RESULTS
  An association was observed between categorized VEGF and p53 overexpression (p=0.022), and between VEGFR-1 and race (p=0.027) or histologic subtype (p=0.007). Unadjusted Cox regression analyses indicated that high compared with low THBS-1, but not VEGF or VEGFR-1, was associated with an increased risk of disease progression (hazard ratio [HR]=2.19; 95% confidence interval [CI]=1.29-3.71; p=0.004) and death (HR=1.93; 95% CI=1.12-3.32; p=0.018) whereas bFGF was associated with a reduced risk of disease progression (HR=0.60; 95% CI=0.36-0.99; p=0.046) and death (HR=0.54; 95% CI=0.32-0.93; p=0.026). After adjusting for prognostic factors including clinical characteristics and p53 overexpression, THBS-1 but not bFGF, VEGF or VEGFR-1 was associated with progression-free and overall survival.
  
  
  CONCLUSIONS
  These data suggest that high THBS-1 is an independent predictor of worse progression-free and overall survival in women with advanced-stage EOC. A larger prospective study is warranted for validation of these findings.
authors.affiliation: DUMC 3079, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA. secor002@mc.duke.edu <secor002@mc.duke.edu>
authors.forename: Angeles Alvarez
authors.initials: AA
authors.lastname: Secord
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.forename: Alan
authors.initials: A
authors.lastname: Hutson
authors.forename: Paula S
authors.initials: PS
authors.lastname: Lee
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Havrilesky
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Grace
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
mesh_terms: D000368:Aged; D042501:Angiogenic Proteins / Q000096:biosynthesis*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D019700:Thrombospondin 1 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis
chemical_list: D042501:Angiogenic Proteins; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D040281:Vascular Endothelial Growth Factor Receptor-1