Detection of MDM2/CDK4 Amplification in Lipomatous Soft Tissue Tumors From Formalin-fixed, Paraffin-embedded Tissue. Issue 2 (February 2015)

• Record Type: Journal Article
• Authors: Creytens, David; van Gorp, Joost; Ferdinande, Liesbeth; Speel, Ernst-Jan; Libbrecht, Louis
• Is Part Of: Applied immunohistochemistry & molecular morphology. Volume 23:Issue 2(2015)
• Publication Date: 2015-02
• Subjects: Diagnostic immunohistochemistry -- Periodicals; Immunohistochemistry -- Periodicals; Cells -- Morphology -- Periodicals; Molecular diagnosis -- Periodicals; 616.079
• DOI: 10.1097/PDM.0000000000000041
• Languages: English
• ISSNs: 1541-2016

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>In this study, the detection of <italic>MDM2</italic> and <italic>CDK4</italic> amplification was evaluated in lipomatous soft tissue tumors using multiplex ligation-dependent probe amplification (MLPA), a PCR-based technique, in comparison with fluorescence in situ hybridization (FISH). These 2 techniques were evaluated in a series of 77 formalin-fixed, paraffin-embedded lipomatous tumors (27 benign adipose tumors, 28 atypical lipomatous tumors/well-differentiated liposarcomas, 18 dedifferentiated liposarcomas, and 4 pleomorphic liposarcomas). Using MLPA, with a cut-off ratio of >2, 36/71 samples (22 atypical lipomatous tumors/well-differentiated liposarcomas, and 14 dedifferentiated liposarcomas) showed <italic>MDM2</italic> and <italic>CDK4</italic> amplification. Using FISH as gold standard, MLPA showed a sensitivity of 90% (36/40) and a specificity of 100% (31/31) in detecting amplification of MDM2 and CDK4 in lipomatous soft tissue tumors. In case of high-level amplification (<italic>MDM2</italic>-<italic>CDK4</italic>/CEP12 ratio >5), concordance was 100%. Four cases of atypical lipomatous tumor/well-differentiated liposarcoma (4/26, 15%) with a low <italic>MDM2</italic> and <italic>CDK4</italic> amplification level (<italic>MDM2</italic>-<italic>CDK4</italic>/CEP12 ratio ranging between 2 and 2.5) detected by FISH showed no amplification by MLPA, although gain of <italic>MDM2</italic> and <italic>CDK4</italic> (ratios ranging between 1.6 and 1.9) was seen with MLPA. No amplification was detected in benign lipomatous tumors and pleomorphic liposarcomas. Furthermore, there was a very high concordance between the ratios obtained by FISH and MLPA. In conclusion, MLPA proves to be an appropriate and straightforward technique for screening <italic>MDM2/CDK4</italic> amplification in lipomatous tumors, especially when a correct cut-off value and reference samples are chosen, and could be considered a good alternative to FISH to determine <italic>MDM2</italic> and <italic>CDK4</italic> amplification in liposarcomas. Moreover, because MLPA, as a multiplex technique, allows simultaneous detection of multiple chromosomal changes of interest, it could be in the future a very reliable and fast molecular analysis on paraffin-embedded material to test for other diagnostically, prognostically, or therapeutically relevant genomic mutations in lipomatous tumors.</p> </sec> </abstract>