Lack of lymphatic vascular specificity of vascular endothelial growth factor receptor 3 in 185 vascular tumors

BACKGROUND. Among the molecules important to angiogenesis and lymphangiogen esis is vascular endothelial growth factor receptor 3 (VEGFR-3), a member o f the receptor tyrosine kinases of endothelial cells. This receptor is expr essed consistently in normal lymphatics, lymphangiomas, and in Kaposi sarco ma, but data regarding other vascular tumors are scant. METHODS. In this study the authors immunohistochemically examined VEGFR-3 e xpression in 82 benign, 31 borderline, and 72 malignant vascular tumors usi ng a monoclonal antibody to VEGFR-3, heat-induced epitope retrieval, and an avidin-biotin-peroxidase detection system. RESULTS. Although normal mesenchymal tissues showed VEGFR-3 only in the lym phatics, benign and malignant vascular tumors and neovascularization of non endothelial tumors showed widespread VEGFR-3 distribution. All lymphangioma s and Kaposi sarcomas showed consistent VEGFR-3 reactivity. Among the heman giomas, spindle cell hemangiomas and 80% of capillary (including all lobula r capillary hemangiomas) were positive whereas the endothelium of cavernous , venous, and epitheloid hemangiomas were positive in a minority of cases ( 20%, 27%, and 33%, respectively). Among the borderline lesions, Kaposiform hemangioendotheliomas were intensely positive whereas epithelioid hemangioe ndotheliomas were positive in 11 of 29 cases (38%). Angiosarcomas showed VE GRF-3 reactivity in the majority of cases (48 of 60 cases; 80%). The nonepi thelioid variants more often were positive (40 of 45 cases; 89%) than the e pithelioid variants, of which 8 of 15 (53%) showed positive tumor cells. No nvascular tumors (including perivascular tumors, other sarcomas, melanomas, carcinomas, and large cell lymphomas) consistently were negative whereas t umor neovascularization commonly was VEGFR-3 positive. CONCLUSIONS. The results of the current study show that although VEGFR-3 sh ows specificity toward lymphatics in normal tissues, this receptor is distr ibuted extensively in benign and malignant vascular tumors and therefore ca n be considered a novel marker in the assessment of endothelial cell differ entiation of Vascular neoplasms. (C) 1999 American Cancer Society.