title: Expression of MYCN in pediatric synovial sarcoma.
abstract: Synovial sarcoma accounts for between 6 and 10% of childhood sarcomas and histological diagnosis can be challenging, even for experienced pathologists. Several other tumors enter the differential diagnosis, including malignant peripheral nerve sheath tumor, Ewing sarcoma/primitive neuroectodermal tumor and undifferentiated sarcoma. Several recent reports utilizing expression array techniques have documented expression of the MYCN oncogene in synovial sarcoma. In order to more fully investigate this finding, a series of 12 synovial sarcomas and 29 other sarcomas (four malignant peripheral nerve sheath tumors, 15 Ewing sarcoma/primitive neuroectodermal tumors, 10 undifferentiated sarcomas) were examined for MYCN expression and gene amplification. By RT-PCR, nine of 12 synovial sarcomas (75%) expressed MYCN. Five synovial sarcomas (42%) expressed MYCN at high levels. Of the other sarcomas, one malignant peripheral nerve sheath tumor (25%) and five Ewing sarcoma/primitive neuroectodermal tumors (33%) expressed MYCN at low levels, and all other cases were negative for MYCN. None of the synovial sarcomas had genomic amplification, suggesting that high MYCN expression levels resulted from epigenetic phenomena. Examination of selected downstream targets of MYCN in synovial sarcoma revealed expression of MCM7 (minichromosome maintenance protein 7) in all synovial sarcomas, and expression of nestin (n=10; 83%), ID2 (inhibitor of DNA binding protein 2) (n=6; 50%) and MRP1 (multidrug resistance protein 1) (n=1; 8%) in a subset of synovial sarcomas. Expression of downstream targets did not correlate with expression of MYCN. Neither MYCN nor expression of downstream targets significantly correlated with metastases at presentation, progression-free survival or overall survival in this small series. In summary, high levels of MYCN expression was useful for distinguishing synovial sarcoma from other childhood-spindled cell sarcomas with specificity and sensitivity of 100 and 42%, respectively, in this series. The clinical and biological significance of this finding deserves further study.
authors.affiliation: Division of Pathology, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada. gino.somers@sickkids.ca
authors.forename: Gino R
authors.initials: GR
authors.lastname: Somers
authors.forename: Maria
authors.initials: M
authors.lastname: Zielenska
authors.forename: Shaker
authors.initials: S
authors.lastname: Abdullah
authors.forename: Christopher
authors.initials: C
authors.lastname: Sherman
authors.forename: Suzanne
authors.initials: S
authors.lastname: Chan
authors.forename: Paul S
authors.initials: PS
authors.lastname: Thorner
mesh_terms: D000293:Adolescent; D018797:Cell Cycle Proteins / Q000378:metabolism; D002648:Child; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D007223:Infant; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D008297:Male; D064168:Minichromosome Maintenance Complex Component 7; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014178:Translocation, Genetic
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051797:Inhibitor of Differentiation Protein 2; D064168:Minichromosome Maintenance Complex Component 7; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; C497450:ID2 protein, human; C459801:MYCN protein, human; C116512:SYT-SSX fusion protein; C101624:MCM7 protein, human; C421109:multidrug resistance-associated protein 1