Proteins involved in regulating bone invasion in skull base meningiomas

Bone invasive skull base meningiomas are a subset of meningiomas that present a unique clinical challenge due to brain and neural structure involvement and limitations in complete surgical resection, resulting in higher recurrence and need for repeat surgery. To date, the pathogenesis of meningioma bone invasion has not been investigated. We investigated immunoexpression of proteins implicated in bone invasion in other tumor types to establish their involvement in meningioma bone invasion. Retrospective review of our database identified bone invasive meningiomas operated on at our institution over the past 20 years. Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1). Differential expression in tumor cell and vasculature was evaluated and comparisons were made between meningioma anatomical locations. MMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells. Noninvasive transbasal meningiomas exhibited higher vascular endothelial cell MMP2 immunoexpression compared to invasive meningiomas. We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas. Strong vascular ITGB1 expression extending from the endothelium through the media and into the adventitia was found in a subset of meningiomas. We have demonstrated that key proteins are differentially expressed in bone invasive meningiomas and that the anatomical location of bone invasion is a key determinant of expression pattern of MMP1, OPN, and ITGB1. This data provides initial insights into the pathophysiology of bone invasion in meningiomas and identifies factors that can be pursued as potential therapeutic targets.