Identification of Epithelial Membrane Protein 2 (EMP2) as a Molecular Marker and Correlate for Angiogenesis in Meningioma

Background: Intracranial meningiomas have been associated with a heterogeneous set of genetic and molecular alterations. Despite these genetic associations, targeted therapies have been unable to increase progression free survival in recurrent or residual meningiomas. There is a need for identification of therapeutic molecular targets in meningioma.

Materials and Methods: Nonpathologic brain tissue from autopsy and tumor specimens from patients undergoing surgical resection for meningioma were collected. Microscopic pathologic analysis, immunohistochemistry and western blot analysis were performed to evaluate EMP2 expression. The NCBI GEO Database was used to evaluate EMP2 mRNA expression data.

Results: EMP2 expression was not identified in normal brain tissue samples from different locations including gray matter, white matter, and meninges in three patients. In comparison, 16 patients with meningioma, there was strong EMP2 staining in 100% of samples (p < 0.001). EMP2 expression was confirmed with western blot in a portion of these samples with 100% positive expressivity and correlated with histologic staining. EMP2 mRNA expression levels were higher in meningioma relative to nonpathologic meninges (p = 0.0013) and brain (p = 0.0011; [Fig. 1]). There was no association between EMP2 levels and WHO grade (p = 0.299) or markers of proliferation (p = 0.797; [Fig. 2]). However, specimens with increased EMP2 were associated with increased angiogenesis on microscopic evaluation (p = 0.059), increased VEGF-A mRNA expression (p < 0.001) and increased clinical markers of tumor vascularity, such as surgical blood loss (p = 0.037; [Fig. 3]).

Conclusion: EMP2 is a protein previously associated with cell migration, invasion, and angiogenesis not identified in normal brain tissue but found in meningioma. It is associated with increased angiogenesis but not tumor proliferation. EMP2 may serve as molecular target for meningioma therapy.

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