Abstract
The adaptor protein NHERF1 (Na/H exchanger-3 regulatory factor-1) and its associated ezrin-radixin-moesin-merlin/neurofibromin-2 (ERM-NF2) family proteins are required for epithelial morphogenesis and have been implicated in cancer progression. NHERF1 is expressed in ependymal cells and constitutes a highly sensitive diagnostic marker for ependymoma, where it labels membrane polarity structures. Since NHERF1 and ERM-NF2 proteins show polarized expression in choroid plexus (CP) cells, we tested their diagnostic utility in CP neoplasms. NHERF1 immunohistochemistry in 43 adult and pediatric tumors with papillary morphology revealed strong apical plasma membrane staining in CP papilloma (WHO grade I) and cytoplasmic expression in CP carcinoma (WHO grade III). Ezrin and moesin showed similar but less distinctive staining. NHERF1 also labeled papillary tumors of the pineal region in a microlumen and focal apical membrane pattern, suggestive of a transitional morphology between CP papilloma and ependymoma. CP tumors of all grades could be differentiated from metastatic carcinomas with papillary architecture by NF2, which showed polarized membranous staining in CP tumors. NHERF1 and NF2 immunohistochemistry showed enhanced sensitivity and specificity for CP tumors compared to commonly used markers, including cytokeratins and Kir7.1, emerging as reliable diagnostic tools for the differential diagnosis of papillary tumors of the central nervous system.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0329-0) contains supplementary material, which is available to authorized users.
Highlights
Choroid plexus (CP) cells are specialized polarized neuroepithelial cells that secrete the cerebrospinal fluid (CSF) and line the intraventricular papillae forming the CP [1]
We found that the distribution of neurofibromin 2 (NF2) can distinguish between CP tumors and papillary metastases, and we endorse using a combination of NHERF1 and NF2 immunohistochemistry (IHC) to address the differential diagnosis for papillary tumors of the central nervous system (CNS)
NHERF1 and NF2 have distinctive expression patterns in CP tumors To understand the role of NHERF1 and ezrin-radixin-moesin-merlin/ neurofibromin-2 (ERM-NF2) proteins in normal and transformed CP, we analyzed their expression by using specific antibodies
Summary
Choroid plexus (CP) cells are specialized polarized neuroepithelial cells that secrete the cerebrospinal fluid (CSF) and line the intraventricular papillae forming the CP [1] These cuboidal cells have domed apical plasma membrane rich in microvilli, basement membrane at the basal pole, and are connected laterally by tight junctions. NHERF1/EBP50 (Na+/H+ exchanger 3 regulating factor 1; ezrin-radixinmoesin (ERM) binding phosphoprotein 50) is an adaptor protein that interacts with solute carriers, such as Na +/H+ exchanger 3, and many other signaling molecules through its amino (N)-terminal PDZ (PSD95-Dlg1-ZO1). Beyond their morphogenetic rolce, both NHERF1 and ERM-NF2 family members are implicated in tumorigenesis.
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