title: Myogenin, AP2β, NOS-1, and HMGA2 are surrogate markers of fusion status in rhabdomyosarcoma: a report from the soft tissue sarcoma committee of the children's oncology group.
abstract: Pediatric rhabdomyosarcoma (RMS) is traditionally classified on the basis of the histologic appearance into alveolar (ARMS) and embryonal (ERMS) subtypes. The majority of ARMS contain a PAX3-FOXO1 or PAX7-FOXO1 gene fusion, but about 20% do not. Intergroup Rhabdomyosarcoma Study stage-matched and group-matched ARMS typically behaves more aggressively than ERMS, but recent studies have shown that it is, in fact, the fusion status that drives the outcome for RMS. Gene expression microarray data indicate that several genes discriminate between fusion-positive and fusion-negative RMS with high specificity. Using tissue microarrays containing a series of both ARMS and ERMS, we identified a panel of 4 immunohistochemical markers-myogenin, AP2β, NOS-1, and HMGA2-which can be used as surrogate markers of fusion status in RMS. These antibodies provide an alternative to molecular methods for identification of fusion-positive RMS, particularly in cases in which there is scant or poor-quality material. In addition, these antibodies may be useful in fusion-negative ARMS as an indicator that a variant gene fusion may be present.
authors.affiliation: *Department of Laboratories, Seattle Children's Hospital #Hematology/Oncology Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA †Department of Biostatistics ‡Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE §Center for Cancer Research, National Cancer Institute, Bethesda, MD ∥Departments of Pathology and Pediatrics, The Ohio State University College of Medicine, Columbus, OH ¶Department Pediatrics Hematology-Oncology, University of Texas Southwestern Medical Center, Dallas, TX **Department of Pathology, Children's Hospital of Boston, Boston, MA ††Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Erin R
authors.initials: ER
authors.lastname: Rudzinski
authors.forename: James R
authors.initials: JR
authors.lastname: Anderson
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Lyden
authors.forename: Julia A
authors.initials: JA
authors.lastname: Bridge
authors.forename: Frederic G
authors.initials: FG
authors.lastname: Barr
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.forename: Karen
authors.initials: K
authors.lastname: Bachmeyer
authors.forename: Stephen X
authors.initials: SX
authors.lastname: Skapek
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Hawkins
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Teot
authors.forename: David M
authors.initials: DM
authors.lastname: Parham
mesh_terms: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D050556:Fatty Acid-Binding Proteins / Q000032:analysis; D025743:HMGA2 Protein / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D018008:Myogenin / Q000032:analysis; D052248:Nitric Oxide Synthase Type I / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051763:PAX7 Transcription Factor / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D025743:HMGA2 Protein; C503799:MYOG protein, human; D018008:Myogenin; D015514:Oncogene Proteins, Fusion; C471563:PAX3-FOXO1A fusion protein, human; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; C497322:Pax7 protein, mouse; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I