The angiogenic growth factors HGF and VEGF in serum and plasma from neuroblastoma patients.
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.
Sköldenberg
Erik G
EG
Department of Surgical Sciences, Section of Pediatric Surgery, University Children's Hospital, Uppsala.
Larsson
Anders
A
Jakobson
Ake
A
Hedborg
Fredrik
F
Kogner
Per
P
Christofferson
Rolf H
RH
Azarbayjani
Faranak
F
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*
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