O1.04ROLE OF AQUAPORIN4 IN HUMAN BRAIN METASTASES: STUDY OF 60 CASES.

Aquaporin4 (AQP4) is the main water channel in the central nervous system and is localized in the astrocytic endfoot processes. AQP4 is involved in important physiological functions, such as water balance and also in neural signal transduction. When the blood-brain barrier become disrupted, as in the case of pathological conditions, such as in brain tumor, water moves from the vasculature into the extracellular space in an AQP4-independent manner, down a hydrostatic gradient to form a vasogenic edema. Moreover, in cancer AQPs have a role promoting tumor progression, invasion and metastasis. The AQP4 contribution to the brain metastasis has not been previously investigated. The aim of our study was to analyze AQP4 distribution in 60 human brain metastases of tumor from lung (n = 20), breast (n = 20), colon (n = 5), kidney (n = 8), melanoma (n = 2), thyroid (n = 1), ovary (n = 3) and prostate (n = 1), using immunohistochemistry and, in some cases western blotting. AQP4 expression on metastasis was related to clinical data of the patients. Our results revealed that: 1) normal brain near metastasis showed an increase of AQP4 expression, accompanied with gliosis; 2) at the metastasis-brain interface, AQP4 staining was increased in all kind of tumor analyzed; 3) AQP4 staining strictly surrounded each metastatic cell, also in some areas in tumor core near vessels, especially in lung and breast; 4) some metastasis from NSCLC showed membrane AQP4 immunostaining. These observations together suggest a beneficial role of AQP4 in the brain edema caused by the metastatic event, indicating that AQP4 expression may restore a normal perivascular rearrangement, also at the periphery of the tumors. Moreover, great AQP4 expression seems to correlate to higher differentiation and a better prognosis. Our findings support to consider AQP4 as a promising therapeutic target.