title: Subtype and prognostic classification of rhabdomyosarcoma by immunohistochemistry.
abstract: OBJECTIVE
  Rhabdomyosarcoma (RMS) is classified into two main subgroups: the embryonal (ERMS) and the alveolar (ARMS) form. The majority of the ARMSs are associated with specific chromosomal translocations (pARMS). Because ARMS is much more aggressive than ERMS, RMS subclassification has clinical relevance. However, diagnosis of RMS subgroups on the basis of histology or molecular biology can be difficult, and supplementing diagnostic methods would be desirable. The aim of this study was to establish a panel of markers for RMS subgroup classification by immunohistochemistry.
  
  
  METHODS
  Gene expression data were used for selection of subgroup-specific markers. Single sections of RMS with available expression data were used for establishment of the immunohistochemistry. Evaluation of the sensitivity and specificity of the markers was carried out using a tissue array representing 252 RMSs. Kaplan-Meier survival curves were calculated for determination of differences in overall survival of the different staining subgroups.
  
  
  RESULTS
  AP2beta and P-cadherin were selected as markers for pARMS, and epidermal growth factor receptor (EGFR) and fibrillin-2 as markers for ERMS. EGFR + fibrillin-2 detected ERMS with a specificity of 90% and with a sensitivity of 60%. AP2beta + P-cadherin detected pARMS with a specificity of 98% and a sensitivity of 64%, and allowed the detection of several misclassified tumors. The EGFR + fibrillin-2-positive group is associated with a favorable outcome, and the AP2beta + P-cadherin-positive group is associated with an unfavorable outcome.
  
  
  CONCLUSIONS
  The presented set of marker proteins detects RMS subgroups with high specificity and may be useful in routine subtype classification of RMS.
authors.affiliation: University Children's Hospital, Division of Oncology, Zurich, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Wachtel
authors.forename: Tina
authors.initials: T
authors.lastname: Runge
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.forename: Sabine
authors.initials: S
authors.lastname: Stegmaier
authors.forename: Ewa
authors.initials: E
authors.lastname: Koscielniak
authors.forename: Jörn
authors.initials: J
authors.lastname: Treuner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Odermatt
authors.forename: Silvia
authors.initials: S
authors.lastname: Behnke
authors.forename: Felix K
authors.initials: FK
authors.lastname: Niggli
authors.forename: Beat W
authors.initials: BW
authors.lastname: Schäfer
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology*; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor