Myogenin is a Specific Marker for Rhabdomyosarcoma: An Immunohistochemical Study in Paraffin-Embedded Tissues

Johns Hopkins University, Baltimore, Maryland, United States
Modern Pathology (Impact Factor: 6.19). 10/2000; 13(9):988-93. DOI: 10.1038/modpathol.3880179
Source: PubMed


Myogenin belongs to a group of myogenic regulatory proteins whose expression determines commitment and differentiation of primitive mesenchymal cells into skeletal muscle. The expression of myogenin has been demonstrated to be extremely specific for rhabdomyoblastic differentiation, which makes it a useful marker in the differential diagnosis of rhabdomyosarcomas (RMS) from other malignant small round cell tumors of childhood. Commercially available antibodies capable of detecting myogenin in routinely processed formalin-fixed paraffin-embedded (FFPE) tissue are now available. In this study, we evaluated myogenin expression using the monoclonal myf-4 antibody (Novocastra Labs) on FFPE in a large number of pediatric tumors in order to define the clinical utility of this marker. A total of 119 tumors were studied. These included 48 alveolar RMS (ARMS), 20 embryonal RMS (ERMS), one spindle cell RMS, 16 Ewing's sarcomas (ES), six nephroblastomas, two ectomesenchymomas, seven precursor hematopoietic neoplasms, five olfactory neuroblastomas, three neuroblastomas, six desmoplastic small round cell tumors, and five rhabdoid tumors. Distinct nuclear staining for myogenin was noted in all 69 RMS. Notably, the number of positive tumor cells differed between the ARMS and ERMS. In ARMS, the majority of tumor cells (75 to 100%) were positive, in contrast to ERMS, in which the positivity ranged from rare + to 25% in all but three tumors. Additionally, myogenin positivity was seen in two of two ectomesenchymomas and in two nephroblastomas with myogenous differentiation. All other tumors were clearly negative. Our results indicate that staining for myogenin is an extremely reliable and specific marker for rhabdomyoblastic differentiation. It gives consistent and easily interpretable results in routinely fixed tissues.

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    • "The expression level of EGFR (Epidermal Growth Factor Receptor) and Fbn2 (Fibrillin-2) as specific markers for eRMS [16,17] were also paradoxically increased in Pax3:Foxo1a,p53,Rb1 tumors. Furthermore, Pax3:Foxo1a,p53,Rb1 tumors also had increased expression of Myogenin, a marker for alveolar and embryonic rhabdomyoblastic differentiation [18], compared with Pax3:Foxo1a,p53 tumors. These results suggested that Rb1 inactivation in the context of Pax3:Foxo1a activation and p53 inactivation may mix the molecular phenotype of tumors for a state neither consistent purely with aRMS or with eRMS. "
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    • "Excess blocking serum was removed and slides were incubated overnight at 4°C with primary antibodies (1∶250 anti-sarcomeric actin, mouse monoclonal IgM, Sigma; 1∶500 anti-smooth muscle actin, mouse monoclonal IgG2a, Sigma, St. Louis, MO; 1∶500 anti-myogenin, mouse monoclonal IgG1, BD Pharmingen, San Diego, CA) diluted in blocking serum. Myogenin was found to be the best marker for RSC immunohistochemistry [47]. Secondary antibodies were Alexa-conjugated fluorochromes 1∶500 IgM-546, 1∶1000 IgG2a-488, 1∶500 IgG1-647 (Molecular Probes, Carlsbad, CA). "
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    • "Immunohistochemistry is the first line supplemental methodology and is sufficient for diagnosis in many cases of small round cell tumors. For example, myogenin and myoD1 are specific and sensitive for the diagnosis of rhabdomyosarcoma [1] and lymphoid markers such as CD20, CD3, CD30 and CD45 are very useful in the diagnosis of lymphoma. However, many other markers, although helpful, are not so specific and require interpretation in the context of an immunohistochemical panel. "
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