103P Molecular and immunohistochemical characterization of radiation-induced breast angiosarcoma

Abstract

Background Angiosarcomas are rare yet highly aggressive malignant tumours originating from vascular endothelial cells. Treatment options are limited, and early diagnosis is critical for patient management. They can be classified into primary and radiation-induced (secondary) angiosarcomas. Secondary angiosarcomas have not yet been fully elucidated in terms of pathogenesis, clinical behaviour, early diagnostic biomarkers, genetic abnormalities and treatment targets. Identification of new biomarkers and therapeutic targets is important for improving the diagnosis and treatment of secondary breast angiosarcomas. This study is focused on secondary breast angiosarcoma arising as a consequence of radiotherapy following breast cancer treatment. These typically occur 5 to 10 years after radiation therapy. The objective of this study was to elucidate the immunohistochemical (IHC) profile of secondary angiosarcoma and determine the gene expression pattern of secondary angiosarcoma by performing RNA-seq analysis. Methods CD34, CD31, FLI-1 and ERG IHC stains were performed on 8 paraffin-embedded breast tissue sections diagnosed as secondary angiosarcoma. A total of 19 fresh frozen tissues were used for the RNAseq analysis of which 13 samples were angiosarcoma tumour tissue, while 6 samples were healthy tissue. Results CD31, CD34, and FLI1 were consistently highly expressed across four of the eight tumour samples, whereas ERG positivity was detected in only one of these four samples. Additionally, one tumour sample exhibited positivity solely for CD34 and FLI1, indicating variability in the expression of endothelial markers across cases. In the RNAseq analyses, 644 differentially expressed genes (DEGs) were identified, with 72 genes upregulated and 572 downregulated in secondary breast angiosarcoma. Gene Ontology (GO) enrichment analysis revealed that these DEGs were predominantly associated with biological processes like metabolism, energy pathways, and protein metabolism. Conclusions The findings presented highlight the heterogeneity in the expression of endothelial markers and transcriptomic profiles in secondary breast angiosarcoma, contributing to our understanding of this rare and aggressive malignancy.