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

Abstract

Introduction 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 in situ hybridisation (FISH) or immunohistochemistry (IHC), can help distinguish lipoma from WDLPS/ALT, and DDLPS from other soft tissue tumours (STT). Objective To determine the utility of MDM2 and CDK4 IHC in the above scenario and compare IHC results with FISH. Methodology 61 lipomatous tumours and mimics were reviewed and subject to MDM and CDK4 FISH and IHC. Cases with MDM2and/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. Results 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. Discussion IHC and FISH sensitivity and specificity for MDM2 and CDK4 were comparable to those published in the literature. 1–3 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.