title: Aberrant expression of tumor suppressor proteins in the Ewing family of tumors.
abstract: BACKGROUND
  Deregulation of tumor suppressor gene function and abrogation of cell cycle control are common features of malignant neoplasms, but corresponding data on Ewing sarcomas and primitive neuroectodermal tumors are relatively scarce. We studied the expression of 4 tumor suppressor proteins in the Ewing family of tumors (EFTs).
  
  
  METHODS
  We examined a series of 20 pediatric EFTs for abnormal expression of p16(INK4a), p14(ARF), p21(WAF1), and pRB by immunohistochemical analysis of pretreatment, nondecalcified archival specimens. Clinical follow up was available in all cases (median, 21 months; range, 5-103 months). Five patients presented with metastatic disease, 8 had no evidence of disease at last follow up, and 12 had an adverse outcome (death or progressive tumor posttherapy).
  
  
  RESULTS
  Twelve cases (60%) demonstrated abnormal expression of at least one tumor suppressor protein. There were 11 cases (55%) with loss of p21(WAF1) expression, 4 (20%) with down-regulation of p16(INK4a), 2 (10%) with absence of pRB, and one case (5%) with loss of p14(ARF) expression. Loss of p16(INK4a) expression correlated with metastatic disease at presentation (P =.026), and showed a trend toward shortened survival (P =.20). The p21(WAF1), p14(ARF), and pRB status was not significantly correlated with either metastatic disease at presentation or outcome.
  
  
  CONCLUSIONS
  Abrogation of the G1 checkpoint was common in this series of EFTs, and down-regulation of p21(WAF1) and p16(INK4a) were the most frequent findings. Loss of p16(INK4a) expression may identify a subset of cases with a more aggressive phenotype.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, USA. aiims1742@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: Maitra
authors.forename: H
authors.initials: H
authors.lastname: Roberts
authors.forename: A G
authors.initials: AG
authors.lastname: Weinberg
authors.forename: J
authors.initials: J
authors.lastname: Geradts
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D004791:Enzyme Inhibitors / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000032:analysis; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016160:Retinoblastoma Protein