JOURNAL ARTICLE
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Vascular endothelial growth factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed lymphatic differentiation, including Kaposi's sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas.

Modern Pathology 2000 Februrary
Recently, a novel monoclonal antibody to vascular endothelial growth factor receptor 3 (VEGFR-3), a tyrosine kinase receptor expressed almost exclusively by lymphatic endothelium in the adult, has been shown to react with a small number of cases of Kaposi's sarcoma (KS) and cutaneous lymphangiomas. We sought to extend these studies to a large number of well-characterized vascular neoplasms to evaluate diagnostic uses of this antibody and to determine whether it defines them in a thematic fashion. Formalin-fixed, paraffin-embedded sections from 70 vascular tumors were immunostained with antibodies to VEGFR-3 von Willebrand factor (vWF), and CD31. Anti-VEGFR-3 was positive in 23 of 24 KS, 8 of 16 angiosarcomas (AS), 6 of 6 kaposiform hemangioendotheliomas, 4 of 4 Dabska tumors, and 2 of 13 hemangiomas. Positively staining angiosarcomas were characterized either by a prominent lymphocytic component, a hobnail endothelial cell similar to that encountered in the Dabska tumor, or spindled areas resembling KS. No VEGFR-3 expression was noted in any cases of epithelioid hemangioendothelioma, pyogenic granuloma, littoral angioma, or stasis dermatitis. vWF expression was seen in 10 of 13 KS; 13 of 14 AS; 4 of 5 kaposiform hemangioendotheliomas; and all Dabska tumors, hemangiomas, lymphangiomas, epithelioid hemangioendotheliomas, vascular malformations, stasis dermatitis, and splenic littoral angiomas. CD31 expression was present in 12 of 13 KS, 13 of 14 AS, and in all other cases. Expression of VEGFR-3 is a very sensitive marker of KS, kaposiform, and Dabska-type hemangioendotheliomas, suggesting that all show at least partial lymphatic endothelial differentiation. Expression of VEGFR-3 does not reliably discriminate KS from AS. However, the expression of VEGFR-3 by certain AS having Kaposi-like areas, a prominent lymphocytic infiltrate, or hobnail endothelium may define subset(s) having phenotypic, if not pathogenetic and biologic, differences.

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