In situ analysis of human menin in normal and neoplastic pancreatic tissues: Evidence for differential expression in exocrine and endocrine cells

Ilaria Cavallari, Donna M. D'Agostino, Tiziana Ferro, Antonio Rosato, Luisa Barzon, Claudio Pasquali, Paola Fogar, Marily Theodoropoulou, Giovanni Esposito, Marco Boscaro, Uberto Pagotto, Elisabetta Tebaldi, Francesco Fallo, Luigi Chieco-Bianchi, Vincenzo Ciminale

Research output: Contribution to journalArticle

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome linked to mutations in the MEN1 gene, which encodes a 610-amino-acid nuclear protein termed menin. Because of the lack of a suitable detection protocol, the in situ expression pattern of menin in human tissues remains to be determined. In this study, we have developed an antimenin monoclonal antibody and an indirect immunofluorescence/laser-scanning microscopy protocol for analyzing menin expression in frozen tissue sections. Because neuroendocrine pancreatic tumors represent a key feature of MEN1, we focused this study on nontumoral pancreas and a small panel of neuroendocrine pancreatic tumors. Results showed that menin was readily detected in nontumoral exocrine cells. In contrast, most islet cells expressing insulin, glucagon, or somatostatin showed considerably weaker levels of menin expression; however, a subpopulation of pancreatic polypeptide-positive cells exhibited a signal comparable with that detected in adjacent exocrine cells. Sporadic endocrine tumors showed variable levels of menin expression, whereas a MEN1-/- gastrinoma scored negative. This report thus provides the first description of the expression pattern of menin in human pancreas in situ and lays the groundwork for further studies of other tissues and tumors.

Original languageEnglish
Pages (from-to)3893-3901
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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    Cavallari, I., D'Agostino, D. M., Ferro, T., Rosato, A., Barzon, L., Pasquali, C., Fogar, P., Theodoropoulou, M., Esposito, G., Boscaro, M., Pagotto, U., Tebaldi, E., Fallo, F., Chieco-Bianchi, L., & Ciminale, V. (2003). In situ analysis of human menin in normal and neoplastic pancreatic tissues: Evidence for differential expression in exocrine and endocrine cells. Journal of Clinical Endocrinology and Metabolism, 88(8), 3893-3901. https://doi.org/10.1210/jc.2002-021840