title: Utility of fluorescence in situ hybridization to detect MDM2 amplification in liposarcomas and their morphological mimics.
abstract: The atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLS) and the de-differentiated liposarcoma (DDLS) represent the most common category of liposarcomas. ALT/WDLSs and DDLSs are often difficult to distinguish from other tumors with similar morphological characteristics. In this study, we investigated whether the detection of amplified or overexpressed murine double-minute 2 (MDM2) can be a useful diagnostic ancillary aid. We used fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) to detect MDM2 amplification and protein overexpression, respectively, in 49 WDLSs, 5 DDLSs, 23 myxoid liposarcomas, 25 benign lipomatous tumors, and 75 spindle and pleomorphic sarcomas. MDM2 amplification was detected in 48 of 49 WDLSs, 5 of 5 DDLSs, 2 of 9 malignant peripheral nerve sheath tumors, and 2 of 10 myxofibrosarcomas. We did not detect MDM2 amplification in any of the benign lipomatous tumors. FISH-mediated detection of MDM2 amplification was the most valuable diagnostic aid for ALT/WDLS, as determined by using the Fisher exact test to compare two different diagnoses of 19 biopsies. On the contrary, unequivocal nuclear overexpression of MDM2 was found in only 10 of 50 ALT/WDLSs. The sensitivity and specificity of MDM2 amplification in distinguishing a DDLS from spindle and pleomorphic sarcomas were 100% and 95%, respectively, while those of MDM2 overexpression were 100% and 87%, respectively. In conclusion, our results indicate that FISH-mediated detection of MDM2 amplification is the most useful adjunct in the diagnosis of both ALT/WDLS and DDLS. However, IHC-mediated detection of MDM2 protein is useful only for the diagnosis of DDLS.
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.forename: Yoh
authors.initials: Y
authors.lastname: Dobashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nojima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Seiko
authors.initials: S
authors.lastname: Sawada-Kitamura
authors.forename: Takeru
authors.initials: T
authors.lastname: Oyama
authors.forename: Akishi
authors.initials: A
authors.lastname: Ooi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D003937:Diagnosis, Differential; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008067:Lipoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008080:Liposarcoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D018208:Liposarcoma, Myxoid / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: FISH; IHC; Liposarcoma; MDM2