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Int J Clin Exp Pathol 2013;6(7):1306-1316

Original Article
Utility of fluorescence in situ hybridization to detect MDM2 amplification in liposarcomas
and their morphological mimics

Hiroaki Kimura, Yoh Dobashi, Takayuki Nojima, Hiroyuki Nakamura, Norio Yamamoto, Hiroyuki Tsuchiya, Hiroko Ikeda, Seiko
Sawada-Kitamura, Takeru Oyama, Akishi Ooi

Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan; Department of
Pathology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; Department of Pathology and Laboratory Medicine, Kanazawa
Medical University, Uchinada, Ishikawa, Japan; Department of Environmental and Preventive Medicine, Graduate School of Medical Science,
Kanazawa University, Kanazawa, Ishikawa, Japan; Section of Diagnostic Pathology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan;
Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan

Received March 24, 2013; Accepted May 3, 2013; Epub June 15, 2013; Published July 1, 2013

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. (IJCEP1303049).

Keywords: Liposarcoma, MDM2, FISH, IHC

Address correspondence to: Akishi Ooi, Department of Molecular and Cellular Pathology, Kanazawa University, 13-1 Takara-machi,
Kanazawa, Ishikawa 920-8640, Japan. Tel: +81-76-265-2192; Fax: +81-76-234-4228; E-mail: aooi@med.kanazawa-u.ac.jp