The utility of MDM2 and CDK4 immunohistochemistry in the diagnosis of lipomatous tumours and correlation with fluorescence in situ Hybridisation

Abstract

<h3>Introduction</h3> Lipomas are characterised by balanced chromosomal rearrangements of 12q13-15 whilst well-differentiated liposarcoma/atypical lipomatous tumour (WDLPS/ALT) and dedifferentiated LPS (DDLPS) have ring and giant chromosomes composed of amplified 12q13-15 sequences. The amplified gene products, (MDM2 and CDK4), detected by fluorescence <i>in situ</i> hybridisation (FISH) or immunohistochemistry (IHC), can help distinguish lipoma from WDLPS/ALT, and DDLPS from other soft tissue tumours (STT). <h3>Objective</h3> To determine the utility of MDM2 and CDK4 IHC in the above scenario and compare IHC results with FISH. <h3>Methodology</h3> 61 lipomatous tumours and mimics were reviewed and subject to MDM and CDK4 FISH and IHC. Cases with MDM2 and/or CDK4/CEP12 signal ratio >1.5 were considered as FISH amplified and positive IHC was defined as strong nuclear staining of >1cells/HPF (x400) or moderate staining of >10% cells. <h3>Results</h3> 13 tumours were reclassified as lipoma, WDLPS or DDLPS from their original diagnoses. The sensitivity/specificity of MDM2 and CDK4 IHC for WDLPS versus lipoma was 0.80/0.91 and 0.40/1.0, respectively, and for DDLPS versus STT was 1.0/0.75 and 0.67/0.83. In three of 20 WDLPS cases and in one of six DDLPS, IHC was positive but FISH was negative. MDM2 and CDK4 IHC and FISH had 87% and 95% concordance, respectively. <h3>Discussion</h3> IHC and FISH sensitivity and specificity for MDM2 and CDK4 were comparable to those published in the literature. MDM2-IHC had better sensitivity but lower specificity than CDK4-IHC in the WDLPS versus lipoma group. Both were found complementary to each other and best results were obtained when IHC was used in conjunction with FISH. A similar trend was observed in the DDLPS versus STT group.