title: Clinical relevance of CD44 cell-surface expression and N-myc gene amplification in a multicentric analysis of 121 pediatric neuroblastomas.
abstract: OBJECTIVE
  In contrast to other human tumors, a repression of the cell-surface glycoprotein CD44 on neuroblastoma is a marker of aggressiveness that usually correlates to N-myc amplification. We thus compared the prognostic value of both markers in the initial staging of 121 children treated for neuroblastoma in collaborative institutions.
  
  
  METHODS
  Frozen samples were analyzed by a rapid and well-standardized technique of immunostaining with monoclonal antibodies (MoAbs) against epitopes in the CD44 constant region.
  
  
  RESULTS
  In this retrospective series, CD44 was expressed on 102 specimens and strongly correlated with favorable tumor stages and histology, younger age, and normal N-myc copy numbers. In univariate analysis, CD44 expression and normal N-myc were the most powerful markers of favorable clinical outcome (P < 10(-6) and chi 2 = 65.40 and P < 10(-6) and chi 2 = 42.56, respectively), but analysis of CD44 affords significant prognostic discrimination in subgroups of patients with or without N-myc-amplified tumors. In the subgroup of stage IV neuroblastomas, CD44 was the only significant prognostic marker (P < .02, chi 2 = 5.76), whereas N-myc status was not discriminant. In multivariate analysis of five factors, ie, N-myc amplification, CD44 expression, age, tumor stage, and histology, the only independent prognostic factors of event-free survival were CD44 expression and tumor stage.
  
  
  CONCLUSIONS
  The analysis of CD44 cell-surface expression must be recommended as an additional biologic marker in the initial staging of the disease.
authors.affiliation: Laboratory of Cell Biology, Centre Léon Bérard, Lyon, France.
authors.forename: V
authors.initials: V
authors.lastname: Combaret
authors.forename: N
authors.initials: N
authors.lastname: Gross
authors.forename: C
authors.initials: C
authors.lastname: Lasset
authors.forename: D
authors.initials: D
authors.lastname: Frappaz
authors.forename: G
authors.initials: G
authors.lastname: Peruisseau
authors.forename: T
authors.initials: T
authors.lastname: Philip
authors.forename: D
authors.initials: D
authors.lastname: Beck
authors.forename: M C
authors.initials: MC
authors.lastname: Favrot
mesh_terms: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors