Lymphangiogenesis is not associated with the expression of the lymphangiogenic factor VEGF-C and its receptor VEGFR-3 in human pituitary adenomas

Lymphangiogenesis, the development of new lymphatic vessels, is a process involved in early metastatic spread of several types of tumors. There are no data available about the density and the formation of lymphatic vessels in normal pituitary, in pituitary adenomas and in pituitary carcinomas, although metastasis formation (e.g. in cervical lymph nodes) has been reported from the latter type of tumors. In this study, we determined lymph vessel numbers by counting vessel cells immunopositive for the lymph endothel marker LYVE-1 in 3 normal human pituitaries and in 39 pituitary adenomas. In addition,the immunohistochemical expression pattern of one of the most important lymphangiogenic factors, VEGF-C, and of its receptor VEGFR-3, was studied. No LYVE-1-positive lymph vessels were detected in the 3 normal pituitaries analyzed, but VEGF-C and VEGFR-3 immunoreactivity was observed in around 10% of the endocrine cells and in few scattered vessels, respectively, suggesting therefore the presence of this receptor in blood endothelial cells. The immunohistochemical analysis of the pituitary tumors revealed lymphatic vessels in 11 tumors, while VEGF-C and VEGFR-3 immunoreactivity was detected in 10 and 22 tumors respectively. Most of the VEGFR-3-positive tumors did not show any LYVE-1 immunoreactivity, indicating that blood vessels may express VEGFR-3 also in tumors. Moreover, no significant correlation was observed between the degree of VEGF-C and VEGFR-3 expression and clinico-biological parameters such as tumor type, tumor grade, proliferation index and lymphatic vessel count. These observations suggest that in pituitary adenomas, the VEGF-C/VEGFR-3 system may not be associated with lymphatic vessels, but may play a role in blood vessel system development. Whether this is different in pituitary carcinomas, needs to be clarified in future studies.