Evaluation of AQP4/TRPV4 Channel Co-expression, Microvessel Density, and its Association with Peritumoral Brain Edema in Intracranial Meningiomas.

Abstract

Apart from VEGF-A pathway activation, the existence of peritumoral edema (PTBE) in meningiomas has been correlated with the expression levels of water transporter aquaporin 4 (AQP4). A novel cooperation of AQP4 with the transient receptor potential isoform 4 (TRPV4), a polymodal swelling-sensitive cation channel, has been proposed for regulating cell volume in glial cells. We investigated AQP4/TRPV4 channel co-expression in meningiomas along with the neovascularization of tumors and associate with PTBE. Immunohistochemical staining for AQP4 and TRPV4 expression was quantitatively analyzed in semi-serial sections of archival tissue from 174 patients. Microvessel density was expressed as microvessel count (MVC). PTBE was measured and edema index (EI) was assessed in 23 patients, based on magnetic resonance images (MRI) whereas mRNA levels of AQP4 and TRPV4 were evaluated in these patients using quantitative real-time PCR. High AQP4 was associated with lower-tumor grade (p\u2009<\u20090.05). AQP4 and TRPV4 were correlated in benign (WHO, grade I) (p\u2009<\u20090.0001) but not in high-grade (WHO, grades II and III) meningiomas (p\u2009>\u20090.05). AQP4/TRPV4 levels were independent of EI and MVC (p\u2009>\u20090.05). In contrast, EI was correlated to MVC (p\u2009=\u20090.02). AQP4/TRPV4 co-expression was detected in both edematous and non-edematous meningiomas. However, most of tumors with larger edema (EI\u2009≥\u20092) demonstrated increased levels of AQP4 and TRPV4. Importantly, peri-meningioma tissue of edematous meningiomas demonstrated significantly increased expression for AQP4 (p\u2009=\u20090.007) but not for TRPV4 (p\u2009>\u20090.05) compared with the main tumor. AQP4 and TRPV4 expression is rather associated with a response to vasogenic edema of meningiomas than with edema formation.