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

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.