CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the abdomen

PLoS One. 2014 Aug 14;9(8):e99452. doi: 10.1371/journal.pone.0099452. eCollection 2014.

Abstract

Background: The absence of CDK4 amplification in liposarcomas is associated with favorable prognosis. We aimed to identify the factors associated with tumor recurrence in patients with well-differentiated (WD) and dedifferentiated (DD) liposarcomas.

Methods: From 2000 to 2010, surgical resections for 101 WD and DD liposarcomas were performed. Cases in which complete surgical resections with curative intent were carried out were selected. MDM2 and CDK4 gene amplification were analyzed by quantitative real-time polymerase chain reaction (Q-PCR).

Results: There were 31 WD and 17 DD liposarcomas. Locoregional recurrence was observed in 11 WD and 3 DD liposarcomas. WD liposarcomas showed better patient survival compared to DD liposarcomas (P<0.05). Q-PCR analysis of the liposarcomas revealed the presence of CDK4 amplification in 44 cases (91.7%) and MDM2 amplification in 46 cases (95.8%). WD liposarcomas with recurrence after surgical resection had significantly higher levels of CDK4 amplification compared to those without recurrence (P = 0.041). High level of CDK4 amplification (cases with CDK4 amplification higher than the median 7.54) was associated with poor recurrence-free survival compared to low CDK4 amplification in both univariate (P = 0.012) and multivariate analyses (P = 0.020).

Conclusions: Level of CDK4 amplification determined by Q-PCR was associated with the recurrence of WD liposarcomas after surgical resection.

MeSH terms

  • Abdominal Neoplasms / genetics*
  • Abdominal Neoplasms / mortality
  • Abdominal Neoplasms / pathology*
  • Abdominal Neoplasms / surgery
  • Adult
  • Aged
  • Cyclin-Dependent Kinase 4 / genetics*
  • Cyclin-Dependent Kinase 4 / metabolism
  • Female
  • Gene Amplification*
  • Humans
  • Liposarcoma / genetics*
  • Liposarcoma / mortality
  • Liposarcoma / pathology*
  • Liposarcoma / surgery
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Treatment Outcome
  • Tumor Burden

Substances

  • Proto-Oncogene Proteins c-mdm2
  • Cyclin-Dependent Kinase 4

Grants and funding

The authors have no support or funding to report.