EXPRESSION OF MYOGENIC REGULATORY PROTEINS (MYOGENIN AND MYOD1) IN SMALL BLUE ROUND-CELL TUMORS OF CHILDHOOD

The distinction of rhabdomyosarcoma (RMS) from other small blue round cell tumors of childhood, such as Ewing's sarcoma/peripheral primitive neuroectodermal tumor (pPNET) and neuroblastoma, continues to present a diagnostic challenge to pathologists. The recent recognition of the master role of myogenic regulatory proteins in skeletal muscle commit ment and differentiation, and the availability of monoclonal antibodie s to two of them (myogenin and MyoD1), has prompted us to test their d iagnostic utility in routinely processed, formalin-fixed, and deparaff inized tissue. Preliminary studies had demonstrated that, with the use of beat-induced epitope retrieval techniques, expression of myogenin and MyoD1 could be documented specifically in nuclei of fetal skeletal muscle by the respective antibodies. We performed a retrospective imm unohistochemical analysis on 72 cases of small blue round cell tumors, including 33 RMSs, 1 metastatic myogenous Wilms' tumor, 26 Ewing's sa rcomas/pPNETs, and 12 neuroblastomas. Nuclear expression of myogenin a nd MyoD1 were both found in 30/33 non-overlapping cases of RMS, with n o significant differences in the sensitivity with respect to histologi cal subtypes, and in 1/1 case of myogenous Wilms' tumor. None of the n euroblastomas or Ewing's sarcomas/pNETs demonstrated positive nuclear staining with either antibody. However, most of the neuroblastomas, an d occasional Ewing's sarcomas/pPNETs, showed variable fibrillary, cyto plasmic immunoreactivity with antibody to MyoD1. We conclude that, wit h the use of microwave-based epitope retrieval, antibodies to myogenin and MyoD1 are both useful markers for the identification of RMS among other small blue round cell tumors of childhood, but antibodies to my ogenin have technical advantages over those to MyoD1, as the latter ma y cross-react with an unknown cytoplasmic antigen in non-muscle cells and tumors.