The application of next-generation sequencing-based molecular diagnostics in endometrial stromal sarcoma

Area of Science:

• Gynecologic Oncology
• Molecular Pathology
• Cancer Genetics

Background:

• Endometrial stromal sarcomas (ESSs) are classified into low-grade and high-grade subtypes, differing in clinical behavior.
• Histology and immunophenotype aid diagnosis, but genetic fusions offer crucial insights: JAZF1 fusions for low-grade ESSs and YWHAE-NUTM2 fusions for high-grade ESSs.

Purpose of the Study:

• To assess the effectiveness of a next-generation sequencing (NGS) assay for identifying ESS-specific gene fusions.
• To evaluate the utility of NGS in analyzing archival formalin-fixed paraffin-embedded (FFPE) tumor samples.

Main Methods:

• An NGS-based fusion transcript detection assay (Archer FusionPlex Sarcoma Panel) was employed.
• The assay targeted YWHAE and JAZF1 fusions in 11 low-grade and 5 high-grade ESSs previously characterized by FISH and/or RT-PCR.
• Seven non-ESS sarcomas served as negative controls.

Main Results:

• The NGS assay successfully identified known ESS gene fusions in all tested cases, correlating with FISH/RT-PCR results.
• Four low-grade ESSs with JAZF1-PHF1 fusions were accurately detected due to the assay's open-ended design.
• No significant ESS fusion candidates were found in the control non-ESS sarcomas, indicating high specificity.

Conclusions:

• The NGS-based gene fusion assay demonstrates high sensitivity and specificity for detecting ESS fusion transcripts.
• This NGS approach provides a valuable tool for the accurate molecular diagnosis of endometrial stromal sarcomas.