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Identification of epithelial membrane protein 2 (EMP2) as a molecular marker and correlate for angiogenesis in meningioma

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Abstract

Purpose

Although intracranial meningiomas are the most common primary brain tumor in adults, treatment options are few and have traditionally been limited to surgical resection and radiotherapy. Additional targeted therapies and biomarkers are needed, especially as complete surgical resection is frequently not feasible in many patients.

Methods

Non-pathologic brain tissue from 3 patients undergoing routine autopsies and tumor specimens from 16 patients requiring surgical resection for meningioma were collected. EMP2 protein expression was evaluated by immunohistochemistry and western blot analysis. EMP2 mRNA expression was also investigated using surgical specimens and validated by analysis of several independent NCBI GEO databases.

Results

EMP2 mRNA expression levels were found to be higher in meningioma relative to non-pathologic meninges (P = 0.0013) and brain (P = 0.0011). Concordantly, strong EMP2 protein expression was demonstrated in 100% of meningioma specimens from all 16 patients, with no observable protein expression in normal brain tissue samples from 3 subjects (P < 0.001). EMP2 expression was confirmed by western blot analysis in five samples, with EMP2 protein intensity positively correlating with histologic staining score (R2 = 0.780; P = 0.047). No association was found between EMP2 mRNA or protein levels and WHO grade or markers of proliferation. However, EMP2 expression was positively associated with an angiomatous pattern on histologic evaluation (P = 0.0597), VEGF-A mRNA expression (P < 0.001), and clinical markers of tumor vascularity such as operative blood loss (P = 0.037).

Conclusions

EMP2 is not found in normal brain tissue, yet has shown consistently high mRNA and protein expression in meningiomas, and may serve as a useful molecular marker for these tumors.

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Acknowledgements

This work was generously supported by Eli & Edythe Broad Stem Cell Institute at UCLA Fellowship (K.P.) NIH/NCI P50-CA211015 (M.W. and W.Y.) and NCI R01 CA163971 (M. W.).

Funding

This work was generously supported by Eli & Edythe Broad Stem Cell Institute at UCLA Fellowship (K.P.) NIH/NCI P50-CA211015 (M.W. and W.Y.) and NCI R01 CA163971 (M. W.).

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Authors and Affiliations

  1. Department of Neurosurgery, University of California, Los Angeles, CA, USA

    Kunal S. Patel, Courtney Duong, Prasanth Romiyo & Isaac Yang

  2. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA

    Sameer Kejriwal, Samasuk Thammachantha, Nina Cherian, William Yong & Madhuri Wadehra

  3. Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA

    Madhuri Wadehra & Isaac Yang

  4. Department of Ophthalmology, University of California, Los Angeles, CA, USA

    Michel M. Sun, Ann Chan & Lynn K. Gordon

  5. Ronald Reagan UCLA Medical Center, David Geffen School of Medicine at UCLA, UCLA Jonsson Comprehensive Cancer Center, 300 Stein Plaza, Ste. 562, 5th Floor Wasserman Bldg., Los Angeles, CA, 90095-6901, USA

    Isaac Yang

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Correspondence to Isaac Yang.

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M.W and L.K.G. are inventors on the University of California patents related to anti-EMP2 monoclonal antibodies.

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Patel, K.S., Kejriwal, S., Sun, M.M. et al. Identification of epithelial membrane protein 2 (EMP2) as a molecular marker and correlate for angiogenesis in meningioma. J Neurooncol 147, 15–24 (2020). https://doi.org/10.1007/s11060-020-03401-2

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