Lack of Lymphangiogenesis Despite Coexpression of VEGF-C and Its Receptor Flt-4 in Uveal Melanoma

• Published in: Investigative ophthalmology & visual science Vol. 42; no. 7; pp. 1422 - 1428
• Main Authors: Clarijs, Ruud, Schalkwijk, Lia, Ruiter, Dirk J, de Waal, Robert M. W
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.06.2001; Association for Research in Vision and Ophtalmology
• Subjects: Biological and medical sciences; Breast Neoplasms - blood supply; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - blood supply; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - pathology; Endothelial Growth Factors - metabolism; Humans; Immunoenzyme Techniques; Lymphatic System - metabolism; Medical sciences; Melanoma - blood supply; Melanoma - metabolism; Melanoma - pathology; Neovascularization, Physiologic; Ophthalmology; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Growth Factor - metabolism; Receptors, Vascular Endothelial Growth Factor; Skin Neoplasms - blood supply; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Tumors and pseudotumors of the eye, orbit, eyelid, lacrimal apparatus; Uveal Neoplasms - blood supply; Uveal Neoplasms - metabolism; Uveal Neoplasms - pathology; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3; Human; Pathophysiology; Uvea disease; Malignant tumor; Metastasis; Lymphatic circulation; Eye disease; Vascular endothelium growth factor; Uvea; Malignant melanoma; Lymphatic dissemination; Blood dissemination; Biological receptor
• ISSN: 0146-0404; 1552-5783

Because lymphatic vessels are absent from the normal eye and because uveal melanomas are presumed to spread by a hematogenous route in the absence of tumor exposure to conjunctival lymphatics, this study was undertaken to investigate the presence of lymphatic vessels in primary uveal melanomas. The presence of lymphatics in 2 control eyes and in 33 primary uveal, 10 primary cutaneous, and 3 metastatic cutaneous melanomas was evaluated by using a double-immunostaining protocol that differentially highlights blood and lymphatic vasculature. In addition, 14 uveal melanomas were immunostained for the lymphatic growth factor vascular endothelial growth factor (VEGF)-C (with anti-VEGF-C polyclonal antibodies [pAbs]), its receptors Flt-4 (with monoclonal antibody [mAb] 9D9) and KDR (with anti-KDR mAb [Clone KDR-2]), and the hemangiogenic factor VEGF-A (with anti-VEGF pAbs). Lymphatics were not detected in normal eyes or in uveal melanoma. As a consequence, signs of lymphangiogenesis were not present. There was coexpression of VEGF-C with Flt-4 and KDR in 6 (43%) of the 14 melanomas. Staining for VEGF-A was completely negative in 25 uveal melanomas analyzed. The strictly hematogenous metastasis of primary uveal melanomas is explained by the absence of lymphatics in and around the tumor. The current data suggest that, in the presence of endothelial Flt-4, VEGF-C expression is not sufficient to induce lymphangiogenesis from preexisting blood vessels in human cancer.