Menin immunoreactivity in secretory granules of human pancreatic islet cells

Larisa V. Debelenko, Sunita Agarwal, Qiang Du, Wusheng Yan, Heidi S. Erickson, Mones Abu-Asab, Mark A. Raffeld, Steven K. Libutti, Stephen J. Marx, Michael R. Emmert-Buck

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The protein product of the Multiple Endocrine Neoplasia Type I (MEN1) gene is thought to be involved in predominantly nuclear functions; however, immunohistochemical (IHC) analysis data on cellular localization are conflicting. To further investigate menin expression, we analyzed human pancreas (an MEN1 target organ) using IHC analyses and 6 antibodies raised against full-length menin or its peptides. In 10 normal pancreas specimens, 2 independently raised antibodies showed unexpected cytoplasmic immunoreactivity in peripheral cells in each islet examined (over 100 total across all 10 patients). The staining exhibited a distinct punctate pattern and subsequent immunoelectron microscopy indicated the target antigen was in secretory granules. Exocrine pancreas and pancreatic stroma were not immunoreactive. In MEN1 patients, unaffected islets stained similar to those in normal samples but with a more peripheral location of positive cells, whereas hyperplastic islets and tumorlets showed increased and diffuse cytoplasmic staining, respectively. Endocrine tumors from MEN1 patients were negative for menin, consistent with a 2-hit loss of a tumor suppressor gene. Secretory granule localization of menin in a subset of islet cells suggests a function of the protein unique to a target organ of familial endocrine neoplasia, although the IHC data must be interpreted with some caution because of the possibility of antibody cross-reaction. The identity, cellular trafficking, and role of this putative secretory granule-form of menin warrant additional investigation.

Original languageEnglish (US)
Pages (from-to)748-755
Number of pages8
JournalApplied Immunohistochemistry and Molecular Morphology
Volume22
Issue number10
DOIs
StatePublished - Jan 1 2014

Keywords

  • Endocrine tumor
  • Human tissue
  • Immunohistochemical analysis
  • Menin localization

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Medical Laboratory Technology

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  • Cite this

    Debelenko, L. V., Agarwal, S., Du, Q., Yan, W., Erickson, H. S., Abu-Asab, M., Raffeld, M. A., Libutti, S. K., Marx, S. J., & Emmert-Buck, M. R. (2014). Menin immunoreactivity in secretory granules of human pancreatic islet cells. Applied Immunohistochemistry and Molecular Morphology, 22(10), 748-755. https://doi.org/10.1097/PAI.0000000000000046