title: Activated growth signaling pathway expression in Ewing sarcoma and clinical outcome.
abstract: BACKGROUND
  In Ewing sarcoma (EWS) most of the research on signaling pathways has been performed on cell lines or animal models. The objective of the current study was to determine the relation between clinical outcome and the expression of proteins involved in active growth signaling pathways.
  
  
  METHODS
  A paraffin-embedded microarray of 45 human primary EWS tissue specimens was stained with the antibodies against c-KIT, AKT, p-AKT, p-mTOR, IGF-1R, IGFBP-3, MAPK, p27(KIP1) , and p70S6 kinase. Immunohistochemical staining was correlated with patient overall survival (OS).
  
  
  RESULTS
  In the univariate analysis 3 variables showed statistical significance to predict survival: presence of metastasis, p-mTOR, and p27(KIP1). A positive stain for p-mTOR (hazard ratio of 4.74 [95% CI (57, 121)]) was significantly (log-rank test with a P = 0.029) associated with better OS. Also, a positive stain for p27(KIP1) (hazard ratio of 6.87 [95% CI (77, 136)] was significantly (log-rank test with a P = 0.009) associated with better OS. Multivariate analysis showed metastasis (HR: 4.3; 95% CI: 0.99, 19; P = 0.05), p-mTOR (HR: 4.8 with 95% CI: 0.6, 38; P = 0.13) and p27 (HR: 5.3; 95% CI: 1.37, 20; P = 0.01) as independent prognostic factors of outcome.
  
  
  CONCLUSIONS
  In our series, p-mTOR and p27(KIP1) protein overexpression were independently associated with better survival.
authors: Department of Oncology, Hospital Sant Joan de Déu, Barcelona, Spain. jmora@hsjdbcn.org
authors: Jaume
authors: J
authors: Mora
authors: Eva
authors: E
authors: Rodríguez
authors: Carmen
authors: C
authors: de Torres
authors: Teresa
authors: T
authors: Cardesa
authors: José
authors: J
authors: Ríos
authors: Teresa
authors: T
authors: Hernández
authors: Antonio
authors: A
authors: Cardesa
authors: Enrique
authors: E
authors: de Alava
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011494:Protein Kinases / Q000096:biosynthesis; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D015398:Signal Transduction; D015996:Survival Rate
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011494:Protein Kinases