Pleomorphic liposarcoma: clinical observations and molecular variables

Cancer. 2011 Dec 1;117(23):5359-69. doi: 10.1002/cncr.26195. Epub 2011 May 19.

Abstract

Background: Pleomorphic liposarcoma (PLS) is a rare high-grade sarcoma that has lipoblastic differentiation. In this study, the authors evaluated PLS natural history, patient outcomes, and commonly deregulated protein biomarkers.

Methods: Medical records from patients (n = 155) who had PLS from 1993 to 2010 were reviewed. Univariate and multivariate analyses were conducted to identify independent prognosticators. A PLS tissue microarray (TMA) (n = 56 patient specimens) was constructed for immunohistochemical analysis of molecular markers, and p53 gene sequencing (exons 5-9) was conducted.

Results: The average patient age was 57 years, and the patients presented with primary disease (n = 102), recurrent disease (n = 16), and metastatic disease (n = 37). Lower extremity was the most common disease site (40%), and the average tumor size was 11 cm. Complete follow-up data were available for 83 patients, and their median follow-up was 22.6 months. The 5-year disease-specific survival rate was 53%; and recurrent disease, unresectability, and microscopic positive margins were identified as predictors of a poor prognosis. Systemic relapse (the strongest poor prognostic determinant) developed in 35% of patients with localized PLS. Immunohistochemical analysis revealed increased expression of peroxisome proliferator-activated receptor gamma (an adipogenic marker), B-cell leukemia 2 and survivin (survival factors), vascular endothelial growth factor (an angiogenic factor), matrix metalloproteinase 2, and other biomarkers. Frequent loss of retinoblastoma protein expression and high p53 mutation rates (approximately 60%) were observed.

Conclusions: PLS is an aggressive, metastasizing sarcoma. Identifying ubiquitous molecular events underlying PLS progression is crucial for progress in patient management and outcomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Female
  • Genes, p53
  • Humans
  • Liposarcoma / chemistry
  • Liposarcoma / genetics*
  • Liposarcoma / mortality
  • Liposarcoma / pathology
  • Male
  • Middle Aged
  • Mutation
  • PPAR gamma / analysis
  • PPAR gamma / physiology
  • Prognosis
  • Proportional Hazards Models
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • PPAR gamma