Immunohistochemical analysis of VEGF-C/VEGFR-3 system and lymphatic vessel extent in normal and adenomatous human pituitary tissues

• Published in: Experimental and clinical endocrinology & diabetes Vol. 116; no. 3; p. 152
• Main Authors: Onofri, C, Losa, M, Uhl, E, Stalla, G K, Renner, U
• Format: Journal Article
• Language: English
• Published: Germany 01.03.2008
• Subjects: Adenoma - metabolism; Adenoma - pathology; Humans; Immunohistochemistry; Lymphangiogenesis - physiology; Lymphatic Vessels - metabolism; Neovascularization, Pathologic - pathology; Pituitary Neoplasms - metabolism; Pituitary Neoplasms - pathology; Reference Values; Vascular Endothelial Growth Factor C - metabolism; Vascular Endothelial Growth Factor Receptor-2 - metabolism
• ISSN: 0947-7349
• DOI: 10.1055/s-2007-992120

The angiogenic growth factor Vascular Endothelial Growth Factor-C (VEGF-C) and its receptor VEGFR-3 are also known to be implicated in the development of lymphatic vessels. We assessed the expression of VEGF-C and VEGFR-3, together with blood and lymphatic vessel extents and proliferation index (PI) values, by immunohistochemistry (IHC) in 6 normal human pituitary glands and 53 pituitary adenomas of different tumour grade, on consecutive tissue sections. VEGF-C was detected in around 10% of the endocrine cells in normal pituitary tissue, while this gland was devoid of lymphatic vascularization and showed very few vessels positive for VEGFR-3. Concerning tumour tissue, most of the adenomas showing VEGF-C immunoreactivity (21/47) were positive in 60% of the tumour cells and the ones positive for VEGFR-3 showed a number of immunostained vessels higher than those observed in the normal pituitary. Most of the tumours positive for VEGFR-3 did not show any LYVE-1 positive vessels (18/53), suggesting that at least in these cases, VEGFR-3 is expressed on blood vessels. Nevertheless, we observed a significant association between low expression of VEGFR-3 and low lymphatic vessel number, suggesting that VEGFR-3 might be involved in the starting of DE NOVO lymphangiogenesis in this tumour type. Moreover, tumours bearing lymphatic vessels showed the tendency to shift towards a more aggressive behaviour (high tumour grade and high PI). In conclusion, the VEGF-C/VEGFR-3 system might be involved in controlling tumour angiogenesis in the pituitary adenomas lacking lymphatic vessels, but may also play a role in starting the process of tumour lymphangiogenesis.