Serum concentrations of vascular endothelial growth factor in angiosarcomas with and without p53 gene mutation.

Sir, Vascular endothelial growth factor (VEGF), a speciŽ c mitogen of endothelial cells in vitro, is also known to induce angiogenesis in vivo. Previous studies have shown that the proliferating cells in vascular tumors, such as angiosarcoma and Kaposi’s sarcoma associated with AIDS, express VEGF mRNA, suggesting that neovascularization supported by VEGF expression in tumor cells is essential for the development and invasion of neoplasia (1–2). VEGF expression is known to be induced through the protein kinase C (PKC) pathway. p53 gene mutation potentiates PKC induction for VEGF expression. p53 gene point mutations have been found in the majority of angiosarcomas (3), and a newly typed p53 gene point mutation has been found in the angiosarcoma cell line ISO-HAS (4). We suggest that these mutations may play an important role in the pathogenesis of angiosarcomas with increased VEGF expression (5, 6). Therefore, the malignant transformation of endothelial cells may be characterized by VEGF expression in the presence of p53 gene mutation. The present study was designed to clarify the association between p53 inactivation and VEGF secretion in cases of angiosarcoma.