MDM2 copy numbers in well-differentiated and dedifferentiated liposarcoma: characterizing progression to high-grade tumors

Am J Clin Pathol. 2014 Mar;141(3):334-41. doi: 10.1309/AJCPLYU89XHSNHQO.

Abstract

Objectives: MDM2 gene amplification is associated with well-differentiated (WDL) and dedifferentiated liposarcomas (DDL). Using fluorescent in situ hybridization (FISH), we sought to characterize various patterns of MDM2 amplification among the morphologic spectrum of liposarcoma.

Methods: Forty-six cases of liposarcoma in various sites were examined and included 22 WDLs, 14 DLLs, and 10 negative control subjects.

Results: The MDM2 amplification ratio (MDM2/CEP12) was lower in WDL (10.2) compared with DDL (18.3) cases (P = .0000002). An amplification ratio of 16 showed optimal sensitivity (0.86) and specificity (0.96) as a cutoff point for progression to DDL. Borderline areas, defined as tumors with increased cellularity and atypia but with preserved lipomatous differentiation, showed a significantly higher MDM2 ratio (17.5; P = .0007) compared with WDL. Central (retroperitoneal and intra-abdominal) tumors also showed a significantly higher MDM2 ratio than peripheral ones (P = .02).

Conclusions: Differences in MDM2 amplification profiles among liposarcomas could help further define and predict progression to high-grade neoplasia.

Keywords: Dedifferentiated liposarcoma; FISH; MDM2; Well-differentiated liposarcoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Cell Differentiation / genetics*
  • DNA Copy Number Variations*
  • Disease Progression
  • Female
  • Humans
  • Liposarcoma / genetics*
  • Liposarcoma / pathology
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-mdm2 / genetics*

Substances

  • Biomarkers, Tumor
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2