Digital Spatial Profiling Demonstrates Differences Between Fibrosarcomatous Transformation of Dermatofibrosarcoma...

Area of Science:

• Oncology
• Dermatopathology
• Molecular Pathology

Background:

• Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer known for local recurrence.
• A subset of DFSP can transform into a higher-grade sarcoma (FST-DFSP), exhibiting more aggressive behavior and metastatic potential.
• Histologic diagnosis of FST-DFSP can be difficult, especially in limited biopsy samples, with no current specific diagnostic markers.

Purpose of the Study:

• To identify molecular markers that distinguish fibrosarcomatous transformation (FST) in DFSP from conventional DFSP.
• To validate the diagnostic utility of identified markers, particularly PRAME, in FST-DFSP using immunohistochemistry.

Main Methods:

• Digital spatial profiling of the transcriptome was performed on tissue microarrays from DFSP and FST-DFSP cases.
• Gene expression data was analyzed to find differentially expressed genes between conventional DFSP and FST-DFSP regions.
• Immunohistochemistry for PRAME was conducted on DFSP and FST-DFSP samples to assess protein expression levels.

Main Results:

• Digital spatial profiling revealed significant gene expression differences between FST-DFSP and conventional DFSP.
• PRAME, CTAG1B, and MMP11 were among the genes significantly overexpressed in FST-DFSP.
• Immunohistochemistry confirmed PRAME overexpression in 70% of FST-DFSP cases versus 4% of conventional DFSP (p<0.0001).

Conclusions:

• Gene expression profiling highlights PRAME and CTAG1B upregulation in FST-DFSP compared to conventional DFSP.
• PRAME immunohistochemistry serves as a valuable tool to support the diagnosis of FST-DFSP, particularly in challenging small biopsies.
• Elevated CTAG1B expression in FST-DFSP suggests potential future therapeutic targets.