ME-16 * IS AQUAPORIN4 (AQP4) INVOLVED IN ADULT HUMAN MEDULLOBLASTOMA DISSEMINATION OR IN A BENEFICIAL BARRIER FORMATION?

Abstract

Medulloblastoma (MDB) is a highly malignant embryonal brain tumor located in the cerebellum with tendency to leptomeningeal dissemination, common in children, rare in adults. Recent genetic analysis suggested classification into four subgroups according to gene expression profiles, including the Wingless signaling pathway-activated group (WNT group), the Sonic Hedgehog signaling pathway-activated group (SHH group), group 3and 4, with distinct molecular, clinicopathological, and prognostic characteristics. AQP4 is the main water channel in the normal central nervous system (CNS) responsible for salt and water balance maintaining. When the blood-brain barrier become disrupted, as in gliomas, water moves from the vasculature into the extracellular space in an AQP4-independent manner, down a hydrostatic gradient to form a vasogenic edema. Moreover, AQPs have a role promoting tumor progression, cell migration and metastasis. Aim of our study was to evaluate for the first time AQP4 expression in adult MDB to focus its role in edema, tumor invasion and dissemination. We analyzed by immunohistochemistry AQP4 expression in 40 adult MDBs, also investigated for GAB1, s-catenin, filamin-A, NPR3, according to molecular subgroups. Desmoplastic histology and Sonic hedgehog (SHH) pathway activation were more common feature, with GAB-1 and filamin-A expression. Only one case showed nuclear staining for s-catenin. None expressed NPR3. In classical MDB, AQP4 staining was localized in glial endfoot surrounding tumor vessels. This AQP4 distribution was lost in the desmoplastic type, where the nodular areas were negatives, surrounded by glial elements AQP4 intensely stained. In the molecular layer of the cerebellar cortex in the tumor proximity in classic type MDB it has been observed migrating tumor cells along glial processes AQP4 stained. This finding was mainly observed in patients with early dissemination. These observations could suggest a role for AQP4 in adult MDB, not only in brain tumor edema resolution, but also in leptomeningeal dissemination.