Detection of MDM2 and CDK4 by Fluorescence In Situ Hyridization, Immunohistochemistry and Real-Time PCR in Liposarcoma: Prognostic Significance Based on the Molecular Diagnosis.
Jun Hun Cho, Jeeyun Lee, Sung Wook Seo, Joon Oh Park, Sung Joo Kim, Geunghwan Ahn, Yoon-La Choi. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Background: The molecular characteristics have been useful in the grouping of liposarcoma. Especially, the amplification MDM2 and CDK4 is the main feature of well-differentiated liposarcomas (WDLs) and dedifferentiated liposarcomas (DDLs). Even though MDM2 and CDK4 are coamplified in most cases, the detailed status has not been elucidated. The aim of this study was to assess the clinical significance based on the status of molecular diagnosis, especially MDM2 and CDK4 amplification.
Design: Eighty three cases of liposarcomas and sixty cases of lipomas diagnosed between 1995 and 2007 were analyzed for the presence of MDM2 amplification using fluorescence in situ hybridization (FISH). MDM2 and CDK4 level also investigated by real-time quantitative PCR (QPCR) and immunohistochemistry. The subtype of liposarcoma was re-classified depending on the results of molecular status. Disease free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log rank test based on the previous histology and re-classified molecular diagnosis.
Results: FISH and QPCR showed highly concordant results. Among 60 lipomas, one case was reclassified as WDL. Three myxoid liposarcomas were reclassified as DDLs and three WDLs as lipomas. The re-classified 79 cases were divided into 38 WDLs, 15 DDLs, 7 pleomorphic liposarcomas (PLs), and 19 myxoid/round cell liposarcomas. Three cases out of 60 MDM2-amplified liposarcomas showed no amplification of CDK4 by QPCR. MDM2 polysomy was detected in FISH and QPCR, especially in the cases of DDLs and PLs. Molecular classification showed better discrimination for the DFS and OS. In the MDM2/CDK4-amplified liposarcomas, CDK4 QPCR level was a significant prognostic factor for DFS but not MDM2 QPCR level.
Conclusions: The use of molecular testing by FISH or QPCR of lipomatous tumors is important to compromise the histology and IHC for the precise grouping of the disease and prediction of the prognosis.
Category: Bone & Soft Tissue
Monday, February 28, 2011 1:00 PM
Poster Session II # 20, Monday Afternoon