title: Differential activation of MAPK and PI3K/AKT/mTOR pathways and IGF1R expression in gastrointestinal stromal tumors.
abstract: OBJECTIVE
  To characterize the differentially-activated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) pathways in mutant (m) and wild-type (wt) GISTs and to investigate the role of insulin-like growth factor 1 receptor (IGF1R) expression.
  
  
  METHODS
  Ninety-nine paraffin-embedded gastrointestinal stromal tumors (GISTs) were selected. CD117, IGF1R, phospho-ERK1/2, phospho-Akt, p70S6, eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and pS6 expression were investigated using immunohistochemical methods. KIT exons 9, 11, 13 and 17 and platelet derived growth factor receptor alpha (PDGFRA) exons 12 and 18 were amplified by PCR and sequenced.
  
  
  RESULTS
  Significant differences were found in the expression of phospho-ERK1/2 between mGISTs and wtGISTs. Complex evaluation of all PI3K/Akt/mTOR pathway markers revealed greater activation in mGISTs, particularly in PDGFRA-mutated GISTs. No significant correlation was observed between IGF1R expression and either mutational status or pathway activation.
  
  
  CONCLUSIONS
  There appears to be no MAPK pathway activation in wtGISTs. Tumors harboring PDGFRA mutations tended to use the PI3K/Akt/mTOR signaling pathway. Most adult GISTs, irrespective of mutational status, displayed no IGFR1 expression; tumors positive for IGFR1 showed no preferential activation of the MAPK or AKT pathways.
authors.affiliation: Department of Pathology, University Hospital Virgen Macarena, Seville, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ríos-Moreno
authors.forename: S
authors.initials: S
authors.lastname: Jaramillo
authors.forename: M
authors.initials: M
authors.lastname: Díaz-Delgado
authors.forename: M
authors.initials: M
authors.lastname: Sánchez-León
authors.forename: I
authors.initials: I
authors.lastname: Trigo-Sánchez
authors.forename: J Polo
authors.initials: JP
authors.lastname: Padillo
authors.forename: J
authors.initials: J
authors.lastname: Amérigo
authors.forename: R
authors.initials: R
authors.lastname: González-Cámpora
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004789:Enzyme Activation; D046152:Gastrointestinal Stromal Tumors / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D011494:Protein Kinases; D017526:Receptor, IGF Type 1; D020928:Mitogen-Activated Protein Kinases