Overexpression of Ets-1 transcription factor in angiosarcoma of the skin.

Angiosarcoma of the skin is a rare malignant tumor which is slow-growing but highly aggressive and often recurs following surgery and/or radiation therapy, finally metastasizing to the regional lymph nodes. The ets-1 protooncogene is shown to be transcribed in endothelial cells during angiogenesis in granulation tissue and in malignant cells during tumor invasion. Furthermore, it can regulate the expression of metalloproteinase genes such as collagenase-1 (MMP-1), stromelysin (MMP-3) and urokinase-type plasminogen activator (uPA). In this study we investigated the ets-1 and MMP-1 expression in 7 angiosarcomas of the skin, compared with 7 hemangiomas and 7 granuloma pyogenicums of the skin, which are well known as benign vascular diseases. The ets-1 and MMP-1 mRNAs and their proteins were overexpressed in all angiosarcomas tested, and the localization of MMP-1 expression corresponded to that of ets-1. On the other hand, they were weakly or not at all expressed in hemangiomas and granuloma pyogenicums. These results suggest that the constitutive overexpression of ets-1 might be closely related with the malignant progression of angiosarcoma, possibly through the up-regulation of the transcription of MMP-1.