Pathogenesis of human hemangiosarcomas and hemangiomas

Hemangiosarcomas are uncommon aggressive vascular tumors that have recently become the focus of attention because several chemicals and pharmaceuticals increase their incidence in mice. The relevance of these mouse vascular tumors to humans is unclear. In the present study, we semiquantitatively evaluated the expression profiles of hematopoietic stem cell markers (CD117 [c-kit], CD133, CD34, and CD45), endothelial cell markers (vascular endothelial growth factor receptor 2, CD31, and factor VIII-related antigen), and a myeloid lineage cell marker (CD14) in human hemangiosarcoma (n = 12) and hemangioma (n = 10) specimens using immunohistochemistry. CD133 was completely negative in almost all cases of hemangiosarcomas and hemangiomas. Most hemangiosarcomas, but not hemangiomas, stained for CD117 and CD45. Both groups diffusely expressed CD34, vascular endothelial growth factor receptor 2, and factor VIII-related antigen; however, hemangiomas had more intense and diffuse CD34 and factor VIII-related antigen expression compared with hemangiosarcomas, whereas CD31 was positive in all hemangiosarcomas but only half of the hemangiomas. CD14 staining was negative in most hemangiosarcoma and hemangioma cases. Our results indicate that multipotential bone marrow-derived hematopoietic stem cells or early endothelial progenitor cells (EPCs) expressing CD117, CD34, and CD45 are involved in hemangiosarcoma formation, whereas hemangiomas originate from late EPCs or differentiated endothelial cells, which have lost the expression of most hematopoietic stem cell markers. This contrasts with our previous results that demonstrated that both hemangiosarcomas and hemangiomas in mice may be derived from early EPCs that are not completely differentiated.