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Overlapping features between dedifferentiated liposarcoma and undifferentiated high-grade pleomorphic sarcoma.

Lawrance Chung1, Sean K Lau, Zhong Jiang

  • 1Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.

The American Journal of Surgical Pathology
|July 4, 2009
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Summary

Dedifferentiated liposarcoma (DDL) and undifferentiated high-grade pleomorphic sarcoma (UHGPS) share markers like CDK4 and MDM2. Gene amplification of these markers helps distinguish DDL from UHGPS, aiding diagnosis.

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Area of Science:

  • Oncology
  • Pathology
  • Molecular Diagnostics

Background:

  • Dedifferentiated liposarcoma (DDL) and undifferentiated high-grade pleomorphic sarcoma (UHGPS) exhibit similar histology and common retroperitoneal/thigh locations.
  • Distinguishing between DDL and UHGPS can be challenging due to overlapping morphologic features.
  • The immunohistochemical and molecular profiles of these two sarcomas are not extensively studied.

Purpose of the Study:

  • To investigate the expression of lipogenic tumor markers peroxisome proliferator-activated receptor gamma (PPAR-gamma), CDK4, and MDM2 in DDL and UHGPS.
  • To determine if these markers and their gene amplification can differentiate between DDL and UHGPS.
  • To assess the diagnostic utility of CDK4 and MDM2 as surrogate markers for malignant lipomatous tumors.

Main Methods:

  • Immunohistochemical analysis of PPAR-gamma, CDK4, and MDM2 expression in 15 DDL and 45 UHGPS cases.
  • Fluorescence in situ hybridization (FISH) to detect MDM2 and CDK4 gene amplification in immunohistochemically positive cases.
  • Correlation of marker expression and gene amplification with tumor type and histologic features.

Main Results:

  • All DDL cases (100%) expressed CDK4 and MDM2; 53% expressed PPAR-gamma.
  • 51% of UHGPS cases expressed at least one of the three markers (PPAR-gamma, CDK4, MDM2).
  • MDM2 and/or CDK4 gene amplification was found in 100% of DDL cases and 13% of UHGPS cases examined by FISH.

Conclusions:

  • CDK4 and MDM2 are sensitive immunohistochemical markers for diagnosing malignant lipomatous tumors.
  • Gene amplification of CDK4 and MDM2 is highly specific for DDL.
  • A subset of UHGPS cases with positive marker expression and gene amplification may represent DDL lacking overt lipoblasts, highlighting the importance of molecular analysis.