NHERF1/EBP50 and NF2 as diagnostic markers for choroid plexus tumors

Maria Magdalena Georgescu, Bret C. Mobley, Brent A. Orr, Ping Shang, Norman L. Lehman, Xiaoping Zhu, Thomas J. O'Neill, Veena Rajaram, Kimmo J. Hatanpaa, Charles F. Timmons, Jack M. Raisanen

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Number of pages1
JournalActa neuropathologica communications
Volume4
Issue number1
DOIs
StatePublished - May 27 2016

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Choroid Plexus Neoplasms
Neurofibromin 2
Choroid Plexus Papilloma
Ependymoma
Staining and Labeling
Immunohistochemistry
Pinealoma
Central Nervous System Neoplasms
Proteins
Choroid Plexus
Membranes
Papillary Carcinoma
Keratins
Morphogenesis
sodium-hydrogen exchanger regulatory factor
Neoplasms
Differential Diagnosis
Cell Membrane
Pediatrics
Sensitivity and Specificity

Keywords

  • Choroid plexus tumors
  • CNS metastases
  • Moesin
  • NF2
  • NHERF1/EBP50
  • Papillary tumor of the pineal region

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

NHERF1/EBP50 and NF2 as diagnostic markers for choroid plexus tumors. / Georgescu, Maria Magdalena; Mobley, Bret C.; Orr, Brent A.; Shang, Ping; Lehman, Norman L.; Zhu, Xiaoping; O'Neill, Thomas J.; Rajaram, Veena; Hatanpaa, Kimmo J.; Timmons, Charles F.; Raisanen, Jack M.

In: Acta neuropathologica communications, Vol. 4, No. 1, 27.05.2016.

Research output: Contribution to journalArticle

Georgescu, Maria Magdalena ; Mobley, Bret C. ; Orr, Brent A. ; Shang, Ping ; Lehman, Norman L. ; Zhu, Xiaoping ; O'Neill, Thomas J. ; Rajaram, Veena ; Hatanpaa, Kimmo J. ; Timmons, Charles F. ; Raisanen, Jack M. / NHERF1/EBP50 and NF2 as diagnostic markers for choroid plexus tumors. In: Acta neuropathologica communications. 2016 ; Vol. 4, No. 1.
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AU - Orr, Brent A.

AU - Shang, Ping

AU - Lehman, Norman L.

AU - Zhu, Xiaoping

AU - O'Neill, Thomas J.

AU - Rajaram, Veena

AU - Hatanpaa, Kimmo J.

AU - Timmons, Charles F.

AU - Raisanen, Jack M.

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AB - 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.

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