title: NHERF1/EBP50 is an organizer of polarity structures and a diagnostic marker in ependymoma.
abstract: NHERF1/EBP50, an adaptor protein required for epithelial morphogenesis, has been implicated in the progression of various human malignancies. NHERF1-deficient mice have intestinal brush border structural defects and we report here that they also have disorganized ependymal cilia with development of non-obstructive hydrocephalus. Examination of mouse and human brain tissues revealed highest NHERF1 expression at the apical plasma membrane of ependymal cells. In ependymal tumors, NHERF1 expression was retained in polarized membrane structures, such as microlumens, rosettes and canals, where it co-localized with some of its ligands, such as moesin and PTEN. Analysis of a comprehensive panel of 113 tumors showed robust NHERF1 labeling of microlumens in 100% of ependymomas, subependymomas, and pediatric anaplastic ependymomas, and in 67% of adult anaplastic ependymomas. NHERF1 staining was present in 35% of ependymoma cases that lacked reactivity for EMA, the routine immunohistochemical marker used for ependymoma diagnosis. NHERF1 labeling of microlumens was either absent or rarely seen in other types of brain tumors analyzed, denoting NHERF1 as a reliable diagnostic marker of ependymal tumors. Anaplastic foci and a subset of adult anaplastic ependymomas showed complete absence of NHERF1-labeled polarity structures, consistent with a loss of differentiation in these aggressive tumors. These data highlight a role for NHERF1 in ependymal morphogenesis with direct application to the diagnosis of ependymal tumors.
authors.forename: Maria-Magdalena
authors.initials: MM
authors.lastname: Georgescu
authors.forename: Paul
authors.initials: P
authors.lastname: Yell
authors.forename: Bret C
authors.initials: BC
authors.lastname: Mobley
authors.forename: Ping
authors.initials: P
authors.lastname: Shang
authors.forename: Theodora
authors.initials: T
authors.lastname: Georgescu
authors.forename: Shih-Hsiu J
authors.initials: SH
authors.lastname: Wang
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
authors.forename: Kimmo J
authors.initials: KJ
authors.lastname: Hatanpaa
authors.forename: Charles L
authors.initials: CL
authors.lastname: White
authors.forename: Jack M
authors.initials: JM
authors.lastname: Raisanen
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016764:Cell Polarity / Q000235:genetics*; D004195:Disease Models, Animal; D004805:Ependyma / Q000473:pathology*; D004806:Ependymoma / Q000175:diagnosis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D006849:Hydrocephalus / Q000175:diagnosis / Q000235:genetics; D007422:Intestines / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D051176:beta Catenin; C093376:sodium-hydrogen exchanger regulatory factor; C071058:moesin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017027:Protein Tyrosine Phosphatases