title: Vascular endothelial growth factor level as a prognostic determinant of small cell lung cancer in Japanese patients.
abstract: OBJECTIVE
  To clarify the clinical significance of vascular endothelial growth factor (VEGF) in Japanese patients with small cell lung cancer (SCLC).
  
  
  METHODS
  We measured serum VEGF levels using an enzyme-linked immunosorbent assay in 45 patients with SCLC before treatment and in 38 patients with benign pulmonary disease and in 32 healthy subjects (71 non-malignant subjects). VEGF immunostaining was performed in tissue biopsies obtained from 23 SCLC patients during bronchoscopic examination.
  
  
  RESULTS
  Median serum VEGF level was 332 pg/ml in patients with SCLC and 160 pg/ml in non-malignant subjects, respectively. The 95% cut-off level to exclude non-malignant subjects was 500 pg/ml. An elevated VEGF level (>500 pg/ml) was found more frequently in patients with extensive disease of SCLC than in those with the limited disease (p<0.01). A significant positive correlation was found between the serum VEGF level and platelet count in SCLC patients (r=0.389; p=0.0083). Serum VEGF level also correlated with serum lactate dehydrogenase in SCLC patients (r=0.381; p=0.0098). However, it did not correlate with serum neuron-specific enolase and pro-gastrin-releasing peptide level. Patients with the elevated VEGF levels had significantly shorter progression-free time than those with the normal VEGF levels (p<0.05). Patients with the elevated VEGF levels had a significantly shorter overall survival time than those with the normal VEGF levels in univariate survival analysis (p<0.05). Further, the elevated VEGF level remained as a significant determinant of poor survival in multivariate analysis (p<0.01). Serum VEGF level was significantly higher in patients with positive VEGF protein immunoreactivity in tumor tissue in SCLC.
  
  
  CONCLUSIONS
  Elevated serum VEGF levels were associated with poor outcome in SCLC.
authors.affiliation: Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Takanashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Okudera
authors.forename: Mika
authors.initials: M
authors.lastname: Kumagai
authors.forename: Akihito
authors.initials: A
authors.lastname: Hayashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morimoto
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000368:Aged; D018288:Carcinoma, Small Cell / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010976:Platelet Count; D011379:Prognosis; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D007770:L-Lactate Dehydrogenase