Combining cadherin expression with molecular markers discriminates invasiveness in GH and PRL pituitary adenomas

Norbert Chauvet, Nicola Romano, Anne-Cécile Meunier, Evelyne Galibert, Pierre Fontanaud, Marie-Noelle Mathieu, Guillaume Osterstock, Philippe Osterstock, Eric Baccino, Valérie Rigau, Hugues Loiseau, Sandrine Bouillot-Eimer, Anne Barlier, Patrice Mollard, Nathalie Coutry

Research output: Contribution to journalArticlepeer-review

Abstract

Although GH- and PRL-secreting pituitary adenomas are considered benign, in many patients, tumor growth and/or invasion constitute a particular challenge. In other tumors, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In this study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumor invasiveness. We have first established, by qPCR and immunohistochemistry, the expression profile of classical cadherins in normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, while N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumors: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalization of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalization of cadherin 18, beta-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumors. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumor invasion.
Original languageEnglish
Article number26686489
JournalJournal of Neuroendocrinology
Volume28
Issue number2
Early online date20 Dec 2015
DOIs
Publication statusPublished - Feb 2016

Keywords

  • Human pituitary tumors
  • Cadherins
  • Epithelial Mesenchymal Transition
  • ESRP
  • Binary tree analysis

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