Oncotarget

Research Papers:

Epithelial differentiation with microlumen formation in meningioma: diagnostic utility of NHERF1/EBP50 immunohistochemistry

Maria-Magdalena Georgescu _, Adriana Olar, Bret C. Mobley, Phyllis L. Faust and Jack M. Raisanen

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Oncotarget. 2018; 9:28652-28665. https://doi.org/10.18632/oncotarget.25595

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Abstract

Maria-Magdalena Georgescu1, Adriana Olar2, Bret C. Mobley3, Phyllis L. Faust4 and Jack M. Raisanen5

1Department of Pathology, Louisiana State University and Feist-Weiller Cancer Center, Shreveport, 71103, LA, USA

2Department of Pathology and Laboratory Medicine and Neurosurgery, Medical University of South Carolina and Hollings Cancer Center, Charleston, 29425, SC, USA

3Department of Pathology, Vanderbilt University Medical Center, Nashville, 37232, TN, USA

4Department of Pathology and Cell Biology, Columbia University, New York, 10032, NY, USA

5Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, 75390, TX, USA

Correspondence to:

Maria-Magdalena Georgescu, email: mmgeorgescu@yahoo.com

Keywords: NHERF1/EBP50; chordoid meningioma; epithelial differentiation; microvilli; NF2

Received: November 27, 2017     Accepted: May 24, 2018     Published: June 19, 2018

ABSTRACT

Meningioma is a primary brain tumor arising from the neoplastic transformation of meningothelial cells. Several histological variants of meningioma have been described. Here we show that NHERF1/EBP50, an adaptor protein required for structuring specialized polarized epithelia, can distinguish meningioma variants with epithelial differentiation. NHERF1 decorates the membrane of intracytoplasmic lumens and microlumens in the secretory variant, consistent with a previously described epithelial differentiation of this subtype. NHERF1 also labels microlumens in chordoid meningioma, an epithelial variant not previously known to harbor these structures, and ultrastructural analysis confirmed the presence of microlumens in this variant. NHERF1 associates with the ezrin-radixin-moesin (ERM)-NF2 cytoskeletal proteins, and moesin but not NF2 was detectable in the microlumens. In a meningioma series from 83 patients, NHERF1 revealed microlumens in 87.5% of the chordoid meningioma (n = 25) and meningioma with chordoid component (n = 7) cases, and in 100% of the secretory meningioma cases (n = 12). The most common WHO grade I meningioma variants lacked microlumens. Interestingly, 20% and 66.6% of WHO grades II (n = 20) and III (n = 3) meningiomas, respectively, showed microlumen-like NHERF1 staining of ultrastructural tight microvillar interdigitations, mainly in rhabdoid, papillary-like or sheeting areas, revealing a new subset of high grade meningiomas with epithelial differentiation. NHERF1 failed to detect microlumens in 12 additional cases of chordoid glioma of the 3rd ventricle, chordoma and chondrosarcoma, neoplasms that may mimic the histological appearance of chordoid meningioma. This study uncovers features of epithelial differentiation in meningioma and proposes NHERF1 immunohistochemistry as a method of discriminating chordoid meningioma from neoplasms with similar appearance.


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