Validation of immature adipogenic status and identification of prognostic biomarkers in myxoid liposarcoma using tissue microarrays

Hum Pathol. 2009 Sep;40(9):1244-51. doi: 10.1016/j.humpath.2009.01.011. Epub 2009 Apr 14.

Abstract

Myxoid liposarcoma displays variably aggressive behavior and responds poorly to available systemic therapies. Expression profiling followed by tissue microarray validation linked to patient outcome is a powerful approach for validating biological mechanisms and identifying prognostic biomarkers. We applied these techniques to independent series of primary myxoid liposarcomas in an effort to assess markers of adipose differentiation in myxoid liposarcoma and to identify prognostic markers that can be efficiently assessed by immunohistochemistry. Candidate genes were selected based on analysis of expression profiles from 9 primary myxoid/round liposarcomas and 45 other soft tissue tumors, and by reference to publicly available data sets. Protein products were validated on an adipose neoplasm tissue microarray, including 32 myxoid liposarcomas linked to patient outcome. Results were scored visually and correlated with clinical outcome by Kaplan-Meier and Cox regression analyses. In the study, by examining expression patterns of several lipogenic regulatory gene products, an immature adipogenic status was verified in myxoid liposarcomas. We also found that expression levels of the ret proto-oncogene, insulin-like growth factor 1 receptor, and insulin-like growth factor 2 correlate with poor metastasis-free survival, supporting a role for ERK/MAPK and PI3K/AKT pathways in clinically aggressive myxoid liposarcomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis*
  • Biomarkers, Tumor / analysis*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Insulin-Like Growth Factor Binding Protein 2 / analysis
  • Kaplan-Meier Estimate
  • Liposarcoma, Myxoid / genetics*
  • Liposarcoma, Myxoid / pathology
  • Liposarcoma, Myxoid / surgery
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-ret / analysis
  • Receptor, IGF Type 1 / analysis
  • Regression Analysis
  • Reproducibility of Results
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / pathology
  • Soft Tissue Neoplasms / surgery
  • Survival Analysis
  • Time Factors
  • Tissue Array Analysis / methods*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Insulin-Like Growth Factor Binding Protein 2
  • Proto-Oncogene Proteins c-ret
  • Receptor, IGF Type 1