title: The angiogenic growth factors HGF and VEGF in serum and plasma from neuroblastoma patients.
abstract: OBJECTIVE
  To determine whether concentrations of the angiogenic growth factors hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A) correlate with clinical and genetic markers in samples taken at diagnosis in children with neuroblastoma (NB).
  
  
  METHODS
  Heparin plasma (P-) and serum (S-) samples of healthy controls (n=73, mean age +/- SD 3.5+/-2.1; females/males: 23/50) and patients with NB (n=62; 2.2+/-1.8; 26/36) were collected between 1988 and 1999. Clinical data included age at diagnosis, gender, stage, outcome, amplification of the oncogene MYCN, loss of heterozygosity at the short arm of chromosome 1 (1p LOH) and ploidy.
  
  
  RESULTS
  HGF and S-VEGF-A were elevated in NB as compared to controls (38/62 patients, p<0.0001 and p<0.05, Mann-Whitney U test). HGF concentrations were higher in high-stage (stage 3-4) as compared to low-stage (stage 1-2) disease (p<0.01). P-HGF was elevated in patients with 1p LOH (p<0.01), MYCN amplification (p<0.001) and di- or tetraploidy (p<0.001). S-HGF concentration was elevated in patients MYCN-amplified tumors only. Plasma and S-HGF concentrations were higher in the deceased group (p<0.05), but not P or S-VEGF-A.
  
  
  CONCLUSIONS
  This study showed that concentrations of HGF and S-VEGF-A are elevated in patients with NB. Furthermore, HGF and S-VEGF-A concentrations correlate to higher stage disease and HGF correlates to genetic markers known to indicate a poor outcome. These observations imply that HGF and VEGF-A have biological roles in NB and suggest the possibility of interference with HGF or VEGF-A signaling as a therapeutic strategy.
authors: Department of Surgical Sciences, Section of Pediatric Surgery, University Children's Hospital, Uppsala.
authors: Erik G
authors: EG
authors: Sköldenberg
authors: Anders
authors: A
authors: Larsson
authors: Ake
authors: A
authors: Jakobson
authors: Fredrik
authors: F
authors: Hedborg
authors: Per
authors: P
authors: Kogner
authors: Rolf H
authors: RH
authors: Christofferson
authors: Faranak
authors: F
authors: Azarbayjani
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019656:Loss of Heterozygosity; D008297:Male; D015337:Multicenter Studies as Topic; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011003:Ploidies; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: C066855:HGF protein, human; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor