Survivin: a novel marker and potential therapeutic target for human angiosarcoma

Summary

Human angiosarcoma is a rare malignant vascular tumor associated with extremely poor clinical outcome and generally arising in the skin of head and neck. However, little is known about the molecular pathogeneses and useful immunohistochemical markers of angiosarcoma. To investigate the mechanisms of angiosarcoma progression, we collected 85 cases of human angiosarcoma specimens with clinical records and used ISO-HAS-B patient derived angiosarcoma cells. As control subjects, 54 cases of hemangioma and 34 of pyogenic granuloma were collected. Remarkably, consistent with our recent observations regarding the involvement of Survivin expression following Hippo pathway inactivation in the neoplastic proliferation of murine hemangioendothelioma cells and human infantile hemangioma, nuclear Survivin expression was observed in all cases of angiosarcoma but not in hemangiomas and pyogenic granulomas and Hippo pathway was inactivated in 90.3% of YAP-positive angiosarcoma cases. However, Survivin expression modes and YAP localization (Hippo pathway activation modes) were not correlated with survival. In addition, we confirmed that Survivin small interference RNA (siRNA) transfection and YM155, an anti-Survivin drug, elicited decreased nuclear Survivin expression and cell proliferation in ISO-HAS-B cells which expressed Survivin consistently. Conclusively, these findings support the importance of Survivin as a good marker and critical regulator of cellular proliferation for human angiosarcoma and YM155 as a potential therapeutic agent.

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