Abstract

BACKGROUND: Glioblastoma multiforme (GBM) is a deadly disease with a survival of approximately 15 months. Epithelial membrane protein 2 (EMP2) is correlated with advanced disease and adverse outcomes in several cancers and has recently been found to be expressed in GBM. Mechanistically, EMP2 promotes αvβ3 integrin surface expression, resulting in an activation of focal adhesion kinase and Src. The consequences of this activation are an increase in tumor growth, cell migration, and invasion. Our preliminary studies suggest that targeting EMP2 with anti-EMP2 antibody results in GBM cell death. METHODS: A custom large tissue microarray (TMA) containing glioma tumor samples from 184 consecutive patients at UCLA was stained for EMP2 expression using human EMP2 antisera. Staining intensity was quantified by an independent pathologist on a 0-3 histological score scale. EMP2 expression level for each sample was correlated with patients' clinical data and outcomes. RESULTS: In the large-scale glioma TMA, EMP2 was expressed strongly in over 90% of GBM samples. EMP2 expression level correlated with increasing grade of glioma, with GBM expressing the highest levels. Furthermore, EMP2 overexpression was significantly associated with increased tumor malignancy and statistically worse patient outcomes. CONCLUSION: Our data presents an extremely novel biomarker and therapeutic target for GBM. These finding suggest that EMP2 expression can be utilized with high validity to determine prognosis in patients with GBM and represents a highly attractive target for anti-glioblastoma therapies. Future prospective, multicenter studies are needed to further validate this large-scale UCLA tissue microarray analysis.

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