title: Real-time polymerase chain reaction analysis of MDM2 and CDK4 expression using total RNA from core-needle biopsies is useful for diagnosing adipocytic tumors.
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).
  
  
  CONCLUSIONS
  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.
authors: Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, 757-1, Asahimachi-dori, Niigata City, Niigata 951-8510, Japan. staro@poplar.ocn.ne.jp.
authors: Taro
authors: T
authors: Sasaki
authors: Akira
authors: A
authors: Ogose
authors: Hiroyuki
authors: H
authors: Kawashima
authors: Tetsuo
authors: T
authors: Hotta
authors: Hiroshi
authors: H
authors: Hatano
authors: Takashi
authors: T
authors: Ariizumi
authors: Hajime
authors: H
authors: Umezu
authors: Riuko
authors: R
authors: Ohashi
authors: Tsuyoshi
authors: T
authors: Tohyama
authors: Naohito
authors: N
authors: Tanabe
authors: Naoto
authors: N
authors: Endo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D062005:Biopsy, Large-Core Needle; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics* / Q000378:metabolism; D020732:Cytogenetic Analysis; D005260:Female; D025743:HMGA2 Protein / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018205:Neoplasms, Adipose Tissue / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D025743:HMGA2 Protein; D015514:Oncogene Proteins, Fusion; D051736:Proto-Oncogene Proteins c-mdm2; D051358:Cyclin-Dependent Kinase 4