title: Expression of insulin-like growth factor system components in Ewing's sarcoma and their association with survival.
abstract: OBJECTIVE
  The role of IGF system in the pathogenesis of Ewing's sarcoma (EWS) is well-documented. However, still little information is available about the value of IGF system components as indicators of prognosis. Understanding the clinical role for IGF system in EWS patients may be important because different subtypes of patients have distinct outcome and may require different treatment protocol. We evaluated the expression of insulin-like growth factor (IGF)-receptor (IGF-IR), insulin receptor (IR), IGF-I and some major intracellular mediators (IRS1, p-ERK) in specimens from EWS patients with primary localised untreated tumours.
  
  
  METHODS
  290 samples were used for immunohistochemistry studies; 57 samples for Real-Time PCR studies; and serum of 67 patients for ELISA.
  
  
  RESULTS
  IGF-IR and IR are expressed in virtually all EWS tumours. Usually both the receptors are present in the same tumour but when one receptor is lacking the other one is always present. Evaluation of IGF-IR, IR and IGF-I with quantitative methods may discriminate differential levels of expression with influences on the patients' outcome. High expression of IGF-IR, IR and IGF-I mRNAs is significantly associated with more favourable clinical outcomes. Higher circulating levels of IGF-I also correlated with lower risk to disease progression and death.
  
  
  CONCLUSIONS
  Overall, our clinical data are in contrast with the assumption that higher amounts of IGF/IGF-IR are a surrogate for higher aggressiveness and indicate that in some cancers the transition to frank malignancy and poor treatment responsiveness seem to be associated with a reduction of IGF system activity.
authors.affiliation: Laboratory of Experimental Oncology, Orthopaedic Institute Rizzoli, Bologna, Italy. katia.scotlandi@ior.it
authors.forename: Katia
authors.initials: K
authors.lastname: Scotlandi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Manara
authors.forename: Massimo
authors.initials: M
authors.lastname: Serra
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Marino
authors.forename: Selena
authors.initials: S
authors.lastname: Ventura
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garofalo
authors.forename: Marco
authors.initials: M
authors.lastname: Alberghini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Magagnoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Lopez-Guerrero
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombard-Bosch
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
mesh_terms: D000293:Adolescent; D002648:Child; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008297:Male; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000378:metabolism* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D007334:Insulin-Like Growth Factor I