EXPRESSION OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR-C RECEPTOR VEGFR-3 IN LYMPHATIC ENDOTHELIUM OF THE SKIN AND IN VASCULAR TUMORS

It is difficult to identify lymph vessels in tissue sections by histoc hemical staining, and thus a specific marker for lymphatic endothelial cells would be more practical in histopathological diagnostics. Here we have applied a specific antigenic marker for lymphatic endothelial cells in the human skin, the vascular endothelial growth factor recept or-3 (VEGFR-3), and show that it identifies a distinct vessel populati on both in fetal and adult skin, which has properties of lymphatic ves sels. The expression of VEGFR-3 was studied in normal human skin by in situ hybridization, iodinated ligand binding, and immunohistochemistr y. A subset of developing vessels expressed the VEGFR-3 mRNA in fetal skin as shown by in situ hybridization and radioiodinated vascular end othelial growth factor (VEGF)-C bound selectively to a subset of vesse ls in adult skin that had morphological characteristics of lymphatic v essels, Monoclonal antibodies against the extracellular domain of VEGF R-3 stained specifically endothelial cells of dermal lymph vessels, in contrast to PBL-E antibodies, which stained only blood vessel endothe lia, In addition, staining for VEGFR-3 was strongly positive in the en dothelium of cutaneous lymphangiomatosis, but staining of endothelial cells in cutaneous hemangiomas was weaker, These results establish the utility of anti-VEGFR-3 antibodies in the identification of lymphovas cular channels in the skin and in the differential diagnosis of skin l esions involving lymphatic or blood vascular endothelium,