title: Elevated serum vascular endothelial growth factor and decreased survival in advanced laryngeal carcinoma.
abstract: OBJECTIVE
  The purpose of this study was to determine whether serum vascular endothelial growth factor (s-VEGF) levels at the time of diagnosis correlate with any known tumor variables and overall survival in patients with advanced laryngeal squamous cell carcinoma. Comparisons with a cohort of normal healthy controls were also performed to determine the potential usefulness of s-VEGF as a screening tool.
  
  
  METHODS
  Serum from patients enrolled in the VA Laryngeal Cooperative Study #258 (n = 183), as well as normal healthy controls (n = 40) was used in this analysis. Quantitative enzyme-linked immunosorbent assays (ELISA) for VEGF were performed in duplicate on each serum sample. Demographic and survival data were available for each patient enrolled in the study. Univariate analyses, multivariate Cox regression analyses, and Kaplan-Meier survival analysis were used.
  
  
  RESULTS
  The mean serum concentration of s-VEGF for the healthy control group was 47.83 +/- 0.13 pg/mL. For all patients enrolled in the VA Cooperative Study, regardless of treatment group, the mean s-VEGF level was 317.22 +/- 25.46 pg/mL. The patients randomly assigned to the surgical arm (n = 97) had a mean value of 315.44 +/- 30.44 pg/mL. Those randomly assigned to the induction chemotherapy arm (n = 86) had a mean s-VEGF level of 319.22 +/- 42.11 pg/mL. Serum VEGF levels were significantly elevated in patients with laryngeal carcinoma compared with healthy controls (p < .001). The serum VEGF levels in each arm of the trial were also elevated versus the healthy controls (p < .001, surgery arm plus radiotherapy; p < .001, chemotherapy plus radiotherapy). In a univariate analysis, elevated s-VEGF correlated with poor Karnofsky performance status for all patients with advanced laryngeal carcinoma (p < .008). High s-VEGF levels also correlated with a poor performance score in patients on the chemotherapy arm of the VA Laryngeal Trial (p < .004). Elevated s-VEGF levels in the surgical plus radiotherapy arm correlated with node-positive disease (p = .047) and supraglottic location of the tumor (p = .022). In a multivariate analysis using all known tumor variables and s-VEGF levels, elevated s-VEGF levels and infiltrating growth pattern correlated with decreased survival for all evaluated patients with advanced laryngeal carcinoma (p = .065, and p = .018, respectively).
  
  
  CONCLUSIONS
  Serum VEGF levels are significantly elevated in patients with advanced laryngeal carcinoma versus healthy controls. Elevated pretreatment s-VEGF levels tended to indicate a more aggressive disease state and a poorer overall survival in advanced laryngeal carcinoma.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, 1500 E Medical Center Dr, Ann Arbor, Michigan 48109-0312, USA. teknos@umich.edu
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.forename: Claudell
authors.initials: C
authors.lastname: Cox
authors.forename: Sirius
authors.initials: S
authors.lastname: Yoo
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
authors.forename: Susan G
authors.initials: SG
authors.lastname: Fisher
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D016022:Case-Control Studies; D015331:Cohort Studies; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors