title: IGF signaling pathway analysis of osteosarcomas reveals the prognostic value of pAKT localization.
abstract: OBJECTIVE
  The aim of this study was to examine the expression of the IGF signaling pathway components in osteosarcoma samples before and after chemotherapy with special emphasis on their prognostic value.
  
  
  METHODS
  Tumor material and follow-up data of 58 osteosarcoma patients were analyzed. Immunohistochemical staining was carried out to identify proteins related to the IGF pathway. Changes in protein expression during treatment, correlations between proteins and subsequent influence on survival were tested.
  
  
  RESULTS
  Proteins of the IGF signaling system are widely expressed in osteosarcoma samples. We demonstrate a change in expression of intracellular pathway proteins after chemotherapy. Remarkably, cytoplasmic pAKT, but not nuclear pAKT, is associated with poor survival.
  
  
  CONCLUSIONS
  IGF pathway proteins seem to be widely activated in osteosarcoma, but their expression changes after chemotherapy. This has implications for the timing of both measuring target expression and pathway interference. Our observations on the prognostic value of cytoplasmic pAKT warrant further investigation while considering the introduction of AKT inhibitors for osteosarcoma treatment.
authors.affiliation: Radboud University Medical Centre, Department of Medical Oncology, Internal Postal Code 452, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Addy C M
authors.initials: AC
authors.lastname: van de Luijtgaarden
authors.forename: Melissa H S
authors.initials: MH
authors.lastname: Roeffen
authors.forename: Manon A
authors.initials: MA
authors.lastname: Leus
authors.forename: Uta E
authors.initials: UE
authors.lastname: Flucke
authors.forename: Bart H W B
authors.initials: BH
authors.lastname: Schreuder
authors.forename: Winette T A
authors.initials: WT
authors.lastname: van der Graaf
authors.forename: Yvonne M H
authors.initials: YM
authors.lastname: Versleijen-Jonkers
mesh_terms: D001859:Bone Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality; D002467:Cell Nucleus / Q000201:enzymology; D018572:Disease-Free Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D012516:Osteosarcoma / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality; D010766:Phosphorylation; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017451:Receptors, Somatomedin / Q000378:metabolism; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D017451:Receptors, Somatomedin; D013002:Somatomedins; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases