title: Circulating concentrations of IGF-I and IGFBP-3 are not predictive of incidence or clinical behavior of pediatric osteosarcoma.
abstract: BACKGROUND
  Preclinical studies suggest a role of insulin-like growth factor-1 (IGF-1) in the proliferation of osteosarcoma cells in vivo. The purpose of this study is to address the relationship between serum levels of IGF-1 and its binding protein (IGFBP-3), and the clinical behavior and outcome of osteosarcoma in children, and to compare those levels present in osteosarcoma patients with a normal population.
  
  
  METHODS
  Serum IGF-1 and IGFBP-3 levels were determined by ELISA in 37 patients with osteosarcoma treated on the same treatment regimen (OS-91 protocol), and who had available serum samples from diagnosis. IGF-1 and IGFBP-3 levels were compared with those previously established in the normal population, matched for age and gender, and were correlated with the presence of metastatic disease, histologic response to preoperative chemotherapy, and event-free survival.
  
  
  RESULTS
  In osteosarcoma patients the median IGF-1 level was 275 ng/ml (range, 105-613) and the median IGFBP-3 level was 3.4 mg/L (range, 2.3-5.1). IGF-1 levels differed from those in the normal population (P = 0.029); although we anticipated higher IGF-1 levels than normal children, 68% of observed standardized scores were less than 0. Furthermore, IGF-1 or IGFBP-3 levels failed to correlate with the presence of metastatic disease (P = 0.12 and P = 0.12, respectively), histologic response (Rosen-Huvos grades 3/4 vs. grades 1/2) (P = 0.95 and P = 0.71, respectively), or event-free survival (P = 0.52 and P = 0.41, respectively). There was a strong association observed between IGF-1 and IGFBP-3 levels (P < 0.001).
  
  
  CONCLUSIONS
  In this retrospective study of 37 patients, we found that circulating levels of IGF-1 and IGFBP-3 are not predictive of the development or clinical characteristics of pediatric osteosarcoma. However, further studies on a larger patient population should be performed in order to investigate this relationship.
authors.affiliation: Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. carlos.rodriquez@stjude.org
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez-Galindo
authors.forename: C A
authors.initials: CA
authors.lastname: Poquette
authors.forename: N C
authors.initials: NC
authors.lastname: Daw
authors.forename: M
authors.initials: M
authors.lastname: Tan
authors.forename: W H
authors.initials: WH
authors.lastname: Meyer
authors.forename: J L
authors.initials: JL
authors.lastname: Cleveland
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I