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

Dermatofibrosarcoma protuberans (DFSP) is a neoplasm of the dermis with a tendency for aggressive local growth and recurrence. A minority of DFSP cases may transform into higher-grade sarcoma (fibrosarcomatous transformation [FST]) (DFSP-FST), which is associated with more aggressive behavior and risk of metastasis. The histologic diagnosis of DFSP-FST may be challenging, particularly in small biopsies. Currently, there are no specific markers to reliably support the diagnosis of DFSP-FST. We identified 33 DFSP from 32 patients, including 9 patients with FST and 1 distant metastasis. Tissue microarrays (TMAs) were created using representative areas of all cases, including DFSP-FST, conventional regions from DFSP-FST, and pure conventional DFSP. Digital spatial profiling of the entire transcriptome was performed on the TMAs using the Nanostring GeoMx platform. Expression data were queried to identify differentially expressed genes specific to the regions of transformation in DFSP. Immunohistochemistry for PReferentially expressed Antigen in MElanoma (PRAME) was subsequently performed using a clinically validated protocol. Digital spatial profiling demonstrated significant gene expression differences between DFSP-FST and conventional DFSP. Genes that were overexpressed in DFSP-FST include PRAME, CTAG1B, and MMP11. Immunohistochemical analysis for PRAME showed positive expression in 7 of 10 DFSP-FST (70%) and 1 of 23 conventional DFSP (4%) (P < .0001). Gene expression profiling shows significant upregulation of PRAME and CTAG1B in DFSP-FST compared with conventional DFSP, a finding that was validated by immunohistochemistry for PRAME. Therefore, immunohistochemistry for PRAME may be useful to support the diagnosis of FST, especially in small biopsies. Increased expression of CTAG1B (NY-ESO-1) in DFSP-FST may also offer future therapeutic potential.