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Open Access Highly Accessed Research article

Real-time polymerase chain reaction analysis of MDM2 and CDK4 expression using total RNA from core-needle biopsies is useful for diagnosing adipocytic tumors

Taro Sasaki1*, Akira Ogose1, Hiroyuki Kawashima1, Tetsuo Hotta1, Hiroshi Hatano3, Takashi Ariizumi3, Hajime Umezu2, Riuko Ohashi2, Tsuyoshi Tohyama4, Naohito Tanabe5 and Naoto Endo1

Author Affiliations

1 Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, 757-1, Asahimachi-dori, Niigata City, Niigata 951-8510, Japan

2 Division of Pathology, Niigata University Medical and Dental Hospital, Niigata, Japan

3 Departments of Orthopedic Surgery, Niigata Cancer Center Hospital, Niigata, Japan

4 Center of Molecular Biology and Cytogenetics, SRL, Inc, Tokyo, Japan

5 Department of Health and Nutrition, Faculty of Human Life Studies, University of Niigata Prefecture, Niigata, Japan

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BMC Cancer 2014, 14:468  doi:10.1186/1471-2407-14-468

Published: 26 June 2014

Abstract

Background

Diagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL.

Methods

A series of lipoma (n = 124) and ALT/WDL (n = 44) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage.

Results

In whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (P < 0.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (P < 0.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: P = 0.6, CDK4: P = 0.8, Wilcoxon signed-rank test).

Conclusion

Quantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.

Keywords:
Liposarcoma; Atypical lipomatous tumor; Adipocytic tumors; MDM2; CDK4; Real-time PCR