Immunohistochemical profile of myogenin and MyoD1 does not support skeletal muscle lineage in alveolar soft part sarcoma.

Department of Pathology, Henry Ford Hospital, Detroit, MI 48202-2689, USA.
Archives of pathology & laboratory medicine (Impact Factor: 2.88). 07/1999; 123(6):503-7. DOI: 10.1043/0003-9985(1999)123<0503:IPOMAM>2.0.CO;2
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Alveolar soft part sarcoma (ASPS) is a soft tissue sarcoma with poor prognosis, and little molecular evidence for its origin, initiation and progression. The aim of this study was to elucidate candidate molecular pathways involved in tumor pathogenesis. We employed high-throughput array comparative genomic hybridization and cDNA-Mediated Annealing, Selection, Ligation, and Extension Assay to profile the genomic and expression signatures of primary and metastatic ASPS from 17 tumors derived from 11 patients. We used an integrative bioinformatics approach to elucidate the molecular pathways associated with ASPS progression. Fluorescence in situ hybridization was performed to validate the presence of the t(X;17)(p11.2;q25) ASPL-TFE3 fusion and hence confirm the aCGH observations. FISH analysis identified the ASPL-TFE3 fusion in all cases. ArrayCGH revealed a higher number of numerical aberrations in metastatic tumors relative to primaries, but failed to identify consistent alterations in either group. Gene expression analysis highlighted 1,063 genes which were differentially expressed between the two groups. Gene set enrichment analysis identified 16 enriched gene sets (p < 0.1) associated with differentially expressed genes. Notable among these were several stem cell gene expression signatures and pathways related to differentiation. In particular, the paired box transcription factor PAX6 was up-regulated in the primary tumors, along with several genes whose mouse orthologs have previously been implicated in Pax6-DNA binding during neural stem cell differentiation. In addition to suggesting a tentative neural line of differentiation for ASPS, these results implicate transcriptional deregulation from fusion genes in the pathogenesis of ASPS.
    Clinical Cancer Research 02/2014; 20(6). DOI:10.1158/1078-0432.CCR-13-2090 · 8.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alveolar soft part sarcoma (ASPS) is a rare, aggressive malignancy of uncertain histological origin with propensity of vascular invasion and distant metastasis. ASPS demonstrates strong predilection for adolescents and young adults with a female preponderance. The head and neck region is the commonly affected region in the pediatric population with orbit and tongue being most common. The indolent clinical course and asymptomatic nature often leads to misdiagnosis and delayed treatment. Herein, we present a case of ASPS affecting the tongue in 14-year-old boy which clinically mimicked hemangioma, common benign vascular tumor of tongue.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alveolar soft part sarcoma (ASPS) commonly arises in the soft tissue of the lower extremities. Primary bone involvement is rare. We report a 23-year-old male who presented with pathologic fracture of the clavicle, and diagnosis of clavicular ASPS. Workup demonstrated a lumbar meningeal mass, also involving the vertebral bodies. Few cases of primary bone ASPS have been identified. Most common primary bone involvement includes the fibula, ilium and tibia. Likewise, meningeal involvement is quite rare. In summary, primary bone ASPS is rare and may involve the clavicle. Meningeal involvement is likewise rare, and presumably represents metastatic spread.
    03/2014; 11(1):48-53. DOI:10.1016/j.jor.2013.12.014