title: Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.
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 (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.
authors: Department of Experimental Medicine, University of L'Aquila, via Vetoio, Coppito 2, 67100 L'Aquila, Italy. jaffrain.ml@libero.it
authors: Marie-Lise
authors: ML
authors: Jaffrain-Rea
authors: Mariolina
authors: M
authors: Angelini
authors: Donatella
authors: D
authors: Gargano
authors: Maria A
authors: MA
authors: Tichomirowa
authors: Adrian F
authors: AF
authors: Daly
authors: Jean-François
authors: JF
authors: Vanbellinghen
authors: Emanuela
authors: E
authors: D'Innocenzo
authors: Anne
authors: A
authors: Barlier
authors: Felice
authors: F
authors: Giangaspero
authors: Vincenzo
authors: V
authors: Esposito
authors: Luca
authors: L
authors: Ventura
authors: Antonietta
authors: A
authors: Arcella
authors: Marily
authors: M
authors: Theodoropoulou
authors: Luciana A
authors: LA
authors: Naves
authors: Carmen
authors: C
authors: Fajardo
authors: Sabina
authors: S
authors: Zacharieva
authors: Vincent
authors: V
authors: Rohmer
authors: Thierry
authors: T
authors: Brue
authors: Alberto
authors: A
authors: Gulino
authors: Giampaolo
authors: G
authors: Cantore
authors: Edoardo
authors: E
authors: Alesse
authors: Albert
authors: A
authors: Beckers
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002648:Child; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010902:Pituitary Gland / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015175:Prolactinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D018336:Receptors, Aryl Hydrocarbon; C103265:aryl hydrocarbon receptor-interacting protein