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.
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.
Folpe AL
，Veikkola T
，Valtola R
，Weiss SW
... -
《MODERN PATHOLOGY》
Kaposi's sarcoma cells of different etiologic origins respond to HIV-Tat through the Flk-1/KDR (VEGFR-2): relevance in AIDS-KS pathology.
Kaposi's sarcoma (KS) is an hyperplastic lesion whose main histological features are typical spindle shaped cells with a mixed endothelial-mesenchymal-macrophage phenotype, an intense vascularization and an inflammatory infiltrate. The etiology of KS appears to be linked to activation of a latent HHV8 infection. Sporadic and iatrogenic KS are slow progressing lesions that can undergo spontaneous regression. In contrast, KS, which is frequently associated with HIV infection, is found in a highly aggressive form in AIDS patients. The HIV-1 Tat has been shown to activate the VEGF receptor KDR in endothelial and KS spindle cells, suggesting this HIV protein could contribute to KS pathogenesis. We used primary 'reactive' KS cell culture from sporadic and epidemic KS, and an immortal KS-line (KS-Imm) isolated in our laboratory from a iatrogenic KS lesion, to verify if Tat-induced cell signaling is able to mediate cellular responses. We demonstrate that KS cells migrated in response to Tat and that VEGF is able to compete with the Tat chemotactic activity towards these cells. A function-blocking anti-KDR antibody was able to abrogate both VEGF and Tat-induced KS chemotactic response, indicating a direct involvement of this receptor. Our data show that HIV-Tat can also activate KS cells derived from sporadic or iatrogenic lesions, suggesting that in AIDS patients Tat could cooperate with VEGF in activation of KDS on KS precursor spindle and endothelial cells, and contribute to the aggressiveness of AIDS-KS lesions.
Morini M
，Benelli R
，Giunciuglio D
，Carlone S
，Arena G
，Noonan DM
，Albini A
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《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》
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