The actin-bundling motility protein fascin and vascular endothelial growth factor (VEGF) are universally over-expressed in human angiosarcoma

Abstract

10068 Background: Angiosarcoma is a highly aggressive soft tissue malignancy with a dismal progression-free survival (PFS). Treatment options for disseminated disease are limited and present systemic therapies have not shown evidence of prolonging overall survival. In this regard, a greater understanding of the molecular and cellular basis of the tumor phenotype of this uncommon malignancy and how these features correlate to clinical behavior would be an important step towards identifying potential new molecular targets for therapy. Our previous work show that acquisition of the chemotherapy-resistant phenotype by angiosarcoma cells occurs concomitantly with a marked increase in cell motility and VEGF expression. Increased expression of the angiogenic factor VEGF and the motility protein fascin have been associated with more aggressive clinical course in a number of other tumor types and may play a direct role in the biologic behavior of these malignancies. Therefore, in the current study, we sought to characterize angiosarcoma by immunohistochemistry for the expression of VEGF and fascin, and compared the staining pattern to benign vascular tumors. Methods: 20 cases of angiosarcoma, and 5 cases of hemangioma were stained for tumor cell expression of VEGF and fascin using anti-VEGF polyclonal antibody (clone A-20, 1:50, Santa Cruz Biotechnology, Santa Cruz, CA) and antibody to fascin (clone 55K-2, 1:500, DakoCytomation, Carpinteria, CA). Results: Surprisingly, every case of angiosarcoma showed high expression for both VEGF and fascin with moderate to strong staining intensity in 75 to 100% of the tumor cells for each case. By comparison, both proteins were either absent or only weakly positive in hemangiomas. Conclusions: In the current study we found high levels of VEGF and fascin universally expressed in angiosarcomas, which was not the case for benign vascular tumors. These factors maybe part of the malignant phenotype for these tumors and contribute to an aggressive clinical course through enhanced cell motility and autocrine/paracrine signaling. Additional study will be needed to better define a role for these proteins in angiosarcoma and to determine if they might represent potential new molecular targets for therapy. No significant financial relationships to disclose.