title: The value of MDM2 and CDK4 amplification levels using real-time polymerase chain reaction for the differential diagnosis of liposarcomas and their histologic mimickers.
abstract: Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL) are reported to have murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) amplification as a characteristic genetic alteration. To evaluate the diagnostic utility of this gene abnormality, we analyzed 19 liposarcomas, 21 malignant fibrous histiocytomas, 3 leiomyosarcomas, 5 malignant peripheral nerve sheath tumors, 23 lipomas, and 28 nonneoplastic fat tissues using real-time polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). In real-time PCR, all ALT/WDLs and DDLs had both MDM2 and CDK4 amplifications. The amplification levels in ALT/WDLs and DDLs were significantly higher than those in the other sarcomas, lipomas, and nonneoplastic fat tissues (P < .05); however, those in the other sarcomas and lipomas were not significantly higher than those in nonneoplastic tissues. In FISH, all ALT/WDLs and DDLs had both MDM2 and CDK4 amplifications, and all of the myxoid/round cell liposarcomas, leiomyosarcomas, malignant peripheral nerve sheath tumors, and all but one of the malignant fibrous histiocytomas did not have the amplifications. In this study, MDM2 and CDK4 amplifications were confirmed in ALT/WDLs and DDLs, and the amplification levels were significantly higher than those in the other tumors. An analysis of MDM2 and CDK4 amplification using real-time PCR, as well as FISH, is useful for the differential diagnosis of liposarcomas and their histologic mimickers.
authors.affiliation: Department of Pathology, Saitama Medical University School of Medicine, Saitama 350-0495, Japan. shio@saitama-med.ac.jp
authors.forename: Shio
authors.initials: S
authors.lastname: Shimada
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishizawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Tadaki
authors.initials: T
authors.lastname: Matsumura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Hirose
mesh_terms: D000273:Adipose Tissue / Q000473:pathology / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D005784:Gene Amplification; D051677:Histiocytoma, Malignant Fibrous / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007890:Leiomyosarcoma / Q000175:diagnosis / Q000235:genetics; D008067:Lipoma / Q000175:diagnosis / Q000235:genetics; D008080:Liposarcoma / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018317:Nerve Sheath Neoplasms / Q000175:diagnosis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051358:Cyclin-Dependent Kinase 4