The microenvironment in sporadic and neurofibromatosis type II related vestibular schwannoma (VS): the same tumor or different? A comparative imaging and neuropathology study

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Abstract

Object: Inflammation and angiogenesis may play a role in the growth of sporadic and neurofibromatosis type II (NF2) related vestibular schwannoma (VS). The similarities in microvascular and inflammatory microenvironment have not been investigated. We sought to compare the tumor microenvironment in sporadic and NF2-related VS using a combined imaging and tissue analysis approach. Methods: Diffusion MR and high-temporal resolution dynamic contrast enhanced (DCE) MRI datasets were prospectively acquired in 20 NF2-related and 24 size matched sporadic VS. Diffusion metrics (mean diffusivity, fractional anisotropy) and DCE-MRI derived microvascular biomarkers (Ktrans, vp, ve, R1N, tumoral blood flow) were compared across both VS groups and regression analysis was used to evaluate the effect of tumor size, pre-treatment tumor growth rate and tumor NF2 status (sporadic vs NF2-related) on each imaging parameter. Tissue from 17 imaged sporadic VS and a separate cohort of 12 NF2-related VS were examined with immunohistochemistry markers for vessels (CD31), vessel permeability (fibrinogen) and macrophage density (Iba1). Expression of VEGF and VEGF receptor 1 (VEGFR-1) was evaluated with immunohistochemistry, western blotting and double immunofluorescence. Results: Imaging data demonstrated DCE-MRI-derived microvascular characteristics were similar in sporadic and NF2-related VS. Ktrans (p<0.001), ve (p≤0.004) and tumoral free water content (p≤0.003) increased with increasing tumor size and pre-treatment tumor growth rate. Regression analysis demonstrated that with the exception of mean diffusivity (p<0.001), NF2 status had no statistically significant effect on each imaging parameter or the observed relationship between imaging parameter and tumor size (p>0.05). Tissue analysis confirmed the imaging metrics amongst resected sporadic VS and demonstrated that across all VS studied, there was a close association between vascularity and Iba1+ macrophage density (r=0.55, p=0.002). VEGF was expressed by Iba1+ macrophages. Discussion: We present the first in vivo comparative study of microvascular and inflammatory characteristics in sporadic and NF2-related VS. Our imaging and tissue analysis results indicate that inflammation is a key contributor to tumor microenvironment and should be viewed as a therapeutic target in both VS groups.

Bibliographical metadata

Original languageEnglish
Pages (from-to)1419-1429
JournalJournal of neurosurgery
Volume134
Issue number5
Publication statusPublished - 29 May 2020