1. ¹Division of Pathology, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada
2. ²Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
3. ³Division of Haematology/Oncology, Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada
4. ⁴Department of Anatomic Pathology, Sunnybrook and Women's College Health Sciences Centre, Toronto, ON, Canada

Correspondence: Dr GR Somers, MBBS, PhD, FRCPA, Division of Pathology, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8. E-mail: gino.somers@sickkids.ca

Received 4 October 2006; Revised 2 March 2007; Accepted 7 March 2007; Published online 27 April 2007.

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.