title: Akt and Hippo Pathways in Ewing's Sarcoma Tumors and Their Prognostic Significance.
abstract: BACKGROUND
  Ewing's sarcoma tumor is an aggressive malignancy of bone and soft tissue in children and young adults. Despite advances in modern therapy, metastasis occurs and results in high mortality. Intracellular molecules Yap, Akt, mTOR, and Erk are signaling pathway members that regulate the proliferation of tumor cells.
  
  
  OBJECTIVE
  We studied the immunohistochemical expression of these proteins in 36 tumor samples from adult and pediatric patients with Ewing's sarcoma tumors. Patients' age, sex, tumor site, tumor size, clinical stage and survival (overall and disease-free survival) were collected. Tissue microarrays slides were stained with antibodies against Yap, Akt, mTOR, and Erk proteins.
  
  
  RESULTS
  Tumors exhibited variable expression of Yap, Akt, mTOR, and Erk (from negative, low to high), with high levels of expression present in 31%, 53%, 77% and 0% respectively. Immunohistochemical expression of Akt was associated with worse overall and disease-free survival (p<0.05). The other biomarkers did not demonstrate any difference in survival between low versus high expression.
  
  
  CONCLUSIONS
  Although Yap, Akt, mTOR, and Erk protein are all expressed in Ewing's sarcoma by immunohistochemistry, only Akt expression is associated with worse prognosis. Larger studies are needed to verify these results and plan targeted therapy, particularly against Akt.
authors.affiliation: 1. Department of Pathology, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Atif A
authors.initials: AA
authors.lastname: Ahmed
authors.affiliation: 1. Department of Pathology, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Malak
authors.initials: M
authors.lastname: Abedalthagafi
authors.affiliation: 2. Department of Epidemiology and Biostatistics, College of Public Health and Health Informatics, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Anwar
authors.affiliation: 3. Department of Anatomic Pathology, Moffitt Cancer Center/University of South Florida, Tampa, Florida, United States.
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Bui
keywords: Akt; Ewing's sarcoma; biomarkers; immunohistochemistry; tissue microarray