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From the Molecular/Cancer Biology Laboratory and Department of
Pathology,*
Haartman Institute, University of Helsinki,
Helsinki, Finland; Ludwig Institute for Cancer
Research§
, Box 240, 5-17177 Stockholm, Sweden;
Department of Pathology,
Brigham and Women's
Hospital and Harvard Medical School, Boston, Massachusetts; and
Department of Pathology,
University Hospital
Nijmegen, Nijmegen, The Netherlands
It is difficult to identify lymph vessels in tissue sections by histochemical 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 receptor-3 (VEGFR-3), and show that it identifies a distinct vessel population both in fetal and adult skin, which has properties of lymphatic vessels. The expression of VEGFR-3 was studied in normal human skin by in situ hybridization, iodinated ligand binding, and immunohistochemistry. A subset of developing vessels expressed the VEGFR-3 mRNA in fetal skin as shown by in situ hybridization and radioiodinated vascular endothelial growth factor (VEGF)-C bound selectively to a subset of vessels in adult skin that had morphological characteristics of lymphatic vessels. Monoclonal antibodies against the extracellular domain of VEGFR-3 stained specifically endothelial cells of dermal lymph vessels, in contrast to PAL-E antibodies, which stained only blood vessel endothelia. In addition, staining for VEGFR-3 was strongly positive in the endothelium 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 lymphovascular channels in the skin and in the differential diagnosis of skin lesions involving lymphatic or blood vascular endothelium.
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R. Valtola, P. Salven, P. Heikkila, J. Taipale, H. Joensuu, M. Rehn, T. Pihlajaniemi, H. Weich, R. deWaal, and K. Alitalo VEGFR-3 and Its Ligand VEGF-C Are Associated with Angiogenesis in Breast Cancer Am. J. Pathol., May 1, 1999; 154(5): 1381 - 1390. [Abstract] [Full Text] [PDF]
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Y. Cao, P. Linden, J. Farnebo, R. Cao, A. Eriksson, V. Kumar, J.-H. Qi, L. Claesson-Welsh, and K. Alitalo Vascular endothelial growth factor C induces angiogenesis in vivo PNAS, November 24, 1998; 95(24): 14389 - 14394. [Abstract] [Full Text] [PDF]
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M. E. Baldwin, B. Catimel, E. C. Nice, S. Roufail, N. E. Hall, K. L. Stenvers, M. J. Karkkainen, K. Alitalo, S. A. Stacker, and M. G. Achen The Specificity of Receptor Binding by Vascular Endothelial Growth Factor-D Is Different in Mouse and Man J. Biol. Chem., May 25, 2001; 276(22): 19166 - 19171. [Abstract] [Full Text] [PDF]
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