Application of MDM2 Fluorescence In Situ Hybridization and Immunohistochemistry in Distinguishing Dedifferentiated Liposarcoma From Other High-grade Sarcomas

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Abstract
Distinguishing dedifferentiated liposarcoma (DDLPS) from other high-grade spindle and pleomorphic sarcomas is important because of better prognosis in case of DDLPS. MDM2 amplification, a genetic abnormality of well-differentiated liposarcoma, is known to be present not only in DDLPS, but also in some other sarcomas. To differentiate DDLPS, we investigated MDM2 amplification and expression in high-grade spindle sarcomas. Eighty-five cases of nonlipogenic high-grade sarcomas, diagnosed between 2008 and 2011, were investigated. Tissue microarray, immunohistochemistry, and fluorescence in situ hybridization for MDM2 were performed. Forty-one of 85 cases (48.2%) showed MDM2 amplification and expression. Cases of MDM2 amplification were reclassified based on histology, immunophenotype, and clinical data. Thirty-nine of 41 cases, including those originally diagnosed as DDLPS (n=30), undifferentiated pleomorphic sarcoma (n=7), myxofibrosarcoma (n=1), and pleomorphic liposarcoma (n=1) could be reclassified as DDLPS. In addition, MDM2 immunohistochemistry and MDM2 fluorescence in situ hybridization showed an excellent correlation (PMDM2 amplification and expression are potentially very useful in distinguishing between DDLPS and other undifferentiated high-grade spindle and pleomorphic sarcomas, even though a few other sarcomas also showed MDM2 amplification and expression.

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