title: Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) is a cytokine that plays an important role in tumor angiogenesis. VEGF is overexpressed in many human cancers, including prostate cancer, but circulating levels of VEGF in patients with prostate cancer have not been reported. In this study, we analyzed plasma concentrations of VEGF in a cohort of patients with prostate cancer and compared them with a normal population.
  
  
  METHODS
  Twenty-six healthy, cancer-free individuals and 80 patients with prostate cancer (54 patients with localized prostate cancer and 26 patients with metastatic prostate cancer [bone or lymph node positive]) were analyzed in this study. Blood was drawn in the same fashion from all individuals and deposited in tubes containing ethylenediaminetetraacetic acid as anticoagulant. Plasma was extracted and VEGF concentrations were determined using a quantitative sandwich enzyme immunoassay technique.
  
  
  RESULTS
  Median plasma VEGF was 28.5 pg/mL (interquartile range 19.3 to 57.0) in patients with metastases; 7.0 pg/mL (interquartile range 0 to 26.5) in patients with localized disease, and 0 pg/mL (interquartile range 0 to 24) in controls. These differences were statistically significant (P <0.001). When compared group by group, the metastatic group had significantly higher plasma VEGF than the localized disease group and the control group (P = 0.003 and P <0.001, respectively). There was a tendency for plasma VEGF to be higher in the localized disease group than in the control group, a trend that almost reached statistical significance (P = 0.038). Using a cutoff of 18 pg/mL, the sensitivity and specificity of the test in differentiating between patients with and without metastatic disease was 81% and 71%, respectively. The odds of metastatic disease were almost 10 times greater for patients with VEGF values greater than 18 pg/mL than for those with values less than 18 pg/mL. There was no correlation between age and plasma VEGF values or between plasma VEGF and serum prostate-specific antigen (PSA). However, patients with serum PSA greater than 20 ng/mL had significantly higher plasma VEGF values than patients with serum PSA less than 20 ng/mL (P <0.001). No direct relation was found between Gleason sum and plasma VEGF, although VEGF levels were higher in patients with Gleason sums of 8 to 10 than in patients with lower Gleason sums.
  
  
  CONCLUSIONS
  Our study indicates that patients with metastatic prostate cancer have higher plasma VEGF levels than patients with localized disease or healthy controls. A larger prospective study is needed to confirm the predictive utility of VEGF.
authors.affiliation: Department of Urology, Children's Hospital, Boston, Massachusetts, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Duque
authors.forename: K R
authors.initials: KR
authors.lastname: Loughlin
authors.forename: R M
authors.initials: RM
authors.lastname: Adam
authors.forename: P W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: D
authors.initials: D
authors.lastname: Zurakowski
authors.forename: M R
authors.initials: MR
authors.lastname: Freeman
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000097:blood* / Q000556:secondary*; D016228:Endothelial Growth Factors / Q000097:blood*; D006801:Humans; D008207:Lymphatic Metastasis; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology; D020033:Protein Isoforms / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors