title: NHERF1/EBP50 and NF2 as diagnostic markers for choroid plexus tumors.
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.
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. mmgeorgescu@yahoo.com.|Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. mmgeorgescu@yahoo.com.
authors.forename: Maria-Magdalena
authors.initials: MM
authors.lastname: Georgescu
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Bret C
authors.initials: BC
authors.lastname: Mobley
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Orr
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Shang
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Lehman
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: O'Neill
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Rajaram
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Kimmo J
authors.initials: KJ
authors.lastname: Hatanpaa
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Timmons
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. jack.raisanen@utsouthwestern.edu.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Raisanen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016545:Choroid Plexus Neoplasms / Q000378:metabolism* / Q000473:pathology; D003937:Diagnosis, Differential; D004806:Ependymoma / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D025581:Neurofibromin 2 / Q000378:metabolism*; D010212:Papilloma / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism*; D012680:Sensitivity and Specificity; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D025581:Neurofibromin 2; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor
keywords: CNS metastases; Choroid plexus tumors; Moesin; NF2; NHERF1/EBP50; Papillary tumor of the pineal region