Article (Scientific journals)
Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.
Jaffrain-Rea, Marie-Lise; Angelini, M.; Gargano, D. et al.
2009In Endocrine-Related Cancer, 16 (3), p. 1029-1043
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Keywords :
Adenoma/genetics/metabolism/pathology; Adolescent; Adult; Child; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins/genetics/metabolism; Middle Aged; Mutation; Neoplasm Invasiveness; Phenotype; Pituitary Gland/metabolism; Pituitary Neoplasms/genetics/metabolism/pathology; Prolactinoma/genetics/metabolism/pathology; Receptors, Aryl Hydrocarbon/genetics/metabolism; Young Adult
Abstract :
[en] 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 (AIP(mut)). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P<0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (P=0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (P=0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP(mut) 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.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Jaffrain-Rea, Marie-Lise
Angelini, M.
Gargano, D.
Tichomirowa, M. A.
Daly, Adrian  ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Vanbellinghen, Jean-François ;  Université de Liège - ULiège > Centre de diagnostic moleculaire
D'Innocenzo, E.
Barlier, Anne
Giangaspero, F.
Esposito, Vincenzina ;  Université de Liège - ULiège > Centre d'études et de rech. sur les macromolécules (CERM)
Ventura, L.
Arcella, A.
Theodoropoulou, M.
Naves, Luciana Ansaneli
Fajardo, C.
Zacharieva, S.
Rohmer, V.
Brue, T.
Gulino, A.
Cantore, G.
Alesse, E.
Beckers, Albert ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
More authors (12 more) Less
Language :
English
Title :
Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.
Publication date :
September 2009
Journal title :
Endocrine-Related Cancer
ISSN :
1351-0088
eISSN :
1479-6821
Publisher :
Society for Endocrinology, Bristol, United Kingdom
Volume :
16
Issue :
3
Pages :
1029-1043
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 May 2010

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