Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: Pathological and clinical implications

Marie Lise Jaffrain-Rea, Mariolina Angelini, Donatella Gargano, Maria A. Tichomirowa, Adrian F. Daly, Jean François Vanbellinghen, Emanuela D'Innocenzo, Anne Barlier, Felice Giangaspero, Vincenzo Esposito, Luca Ventura, Antonietta Arcella, Marily Theodoropoulou, Luciana A. Naves, Carmen Fajardo, Sabina Zacharieva, Vincent Rohmer, Thierry Brue, Alberto Gulino, Giampaolo CantoreEdoardo Alesse, Albert Beckers

Research output: Contribution to journalArticlepeer-review

Abstract

Germline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (n=103), including 17 with AIP mutations (AIPmut). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (Pmut PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype.

Original languageEnglish
Pages (from-to)1029-1043
Number of pages15
JournalEndocrine-Related Cancer
Volume16
Issue number3
DOIs
Publication statusPublished - Sep 2009

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

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