Immunohistochemical profile of Myogenin and MyoD1 does not support skeletal muscle lineage in alveolar soft part sarcoma: A study of 19 tumors

Department of Pathology, Henry Ford Hospital, Detroit, MI 48202-2689, USA.
Archives of pathology & laboratory medicine (Impact Factor: 2.84). 07/1999; 123(6):503-7. DOI: 10.1043/0003-9985(1999)123<0503:IPOMAM>2.0.CO;2
Source: PubMed


The histogenesis of alveolar soft part sarcoma remains elusive. Myogenic origin is favored, although conflicting data on immunohistochemical demonstration of muscle-associated markers exist. Myogenin and MyoD1, transcription factors of the myogenic determination family, have crucial roles in commitment and differentiation of mesenchymal progenitor cells to myogenic lineage and in maintenance of skeletal muscle phenotype. Their immunohistochemical detection is specific in characterization of rhabdomyosarcoma.
Antibodies for myogenin, MyoD1, desmin, and muscle-specific actin were employed on a large series of cases (n = 19) of formalin-fixed, paraffin-embedded alveolar soft part sarcoma.
Minimal scattered nuclear staining was seen with myogenin. All cases had pronounced, nonspecific granular cytoplasmic immunostaining with MyoD1; nuclei were negative. All tumors were negative for desmin and muscle-specific actin. Ultrastructural study in 10 cases failed to reveal features of skeletal muscle differentiation.
Cytoplasmic staining with MyoD1 in alveolar soft part sarcoma may correspond to cross-reactivity with an undetermined cytoplasmic antigen. The lack of immunostaining with myogenin, MyoD1, desmin, and muscle-specific actin provides evidence against a myogenic origin for alveolar soft part sarcoma.

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    • "To date, the definitive origin of this tumor remains unknown. There is some immunohistochemical evidence suggesting that ASPS may arise from striated muscle or pericytes, this remains controversial [12–15]. Primary ASPS tumor sites have also been reported in tissues where skeletal muscle is absent, such as in the stomach, breast tissue, and the female genital tract [16–18]. "
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    ABSTRACT: Alveolar soft part sarcoma (ASPS) is a very rare soft tissue sarcoma which arises primarily in children and young adults. Despite its unique histology and well-characterized genetic translocation, many questions remain regarding the pathogenesis and treatment of this tumor type. Though collective clinical experience with this tumor type spans more than 60 years, there has been little progress made in treating this uncommon but frequently fatal disease. This paper focuses on the available data regarding its molecular pathogenesis and insights into targeted therapeutics as well as the results of clinical trials performed to date to hopefully improve the outcome of patients with this rare malignancy.
    Sarcoma 04/2012; 2012(1):428789. DOI:10.1155/2012/428789
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    • "In spite of several reports suggesting ASPS arises from a myogenic progenitor, the tissue ontogeny of ASPS is still contested, primarily because consistent detection of muscle markers (e.g. MYOD1 or MYOG) has not been demonstrated [5,6]. ASPS cells also contain numerous periodic acid Schiff-positive, diastase-resistant crystalline structures, recently identified as containing monocarboxylate transporter 1 (MCT1) and the cellular chaperone CD147 [7]. "
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    ABSTRACT: Alveolar soft-part sarcoma (ASPS) is an extremely rare, highly vascular soft tissue sarcoma affecting predominantly adolescents and young adults. In an attempt to gain insight into the pathobiology of this enigmatic tumor, we performed the first genome-wide gene expression profiling study. For seven patients with confirmed primary or metastatic ASPS, RNA samples were isolated immediately following surgery, reverse transcribed to cDNA and each sample hybridized to duplicate high-density human U133 plus 2.0 microarrays. Array data was then analyzed relative to arrays hybridized to universal RNA to generate an unbiased transcriptome. Subsequent gene ontology analysis was used to identify transcripts with therapeutic or diagnostic potential. A subset of the most interesting genes was then validated using quantitative RT-PCR and immunohistochemistry. Analysis of patient array data versus universal RNA identified elevated expression of transcripts related to angiogenesis (ANGPTL2, HIF-1 alpha, MDK, c-MET, VEGF, TIMP-2), cell proliferation (PRL, IGFBP1, NTSR2, PCSK1), metastasis (ADAM9, ECM1, POSTN) and steroid biosynthesis (CYP17A1 and STS). A number of muscle-restricted transcripts (ITGB1BP3/MIBP, MYF5, MYF6 and TRIM63) were also identified, strengthening the case for a muscle cell progenitor as the origin of disease. Transcript differentials were validated using real-time PCR and subsequent immunohistochemical analysis confirmed protein expression for several of the most interesting changes (MDK, c-MET, VEGF, POSTN, CYP17A1, ITGB1BP3/MIBP and TRIM63). Results from this first comprehensive study of ASPS gene expression identifies several targets involved in angiogenesis, metastasis and myogenic differentiation. These efforts represent the first step towards defining the cellular origin, pathogenesis and effective treatment strategies for this atypical malignancy.
    BMC Cancer 02/2009; 9(1):22. DOI:10.1186/1471-2407-9-22 · 3.36 Impact Factor
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    ABSTRACT: 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.
    Modern Pathology 10/2000; 13(9):988-93. DOI:10.1038/modpathol.3880179 · 6.19 Impact Factor
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