Jaffrain Rea ML, Angelini M, Gargano D, Tichomirowa M, Daly A, Vanbellinghen JF, D'Innocenzo E, Barlier A, Giangaspero F, Esposito V, Ventura L, Arcella A, Theodoropoulou M, Naves L, Fajardo C, Zacharieva S, Rohmer V, Brue T, Gulino A, Cantore G, Alesse E, Beckers A
Expression of aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor interacting protein (AIP) in pituitary adenomas: pathological and clinical implications. [JOURNAL ARTICLE]
Endocr Relat Cancer 2009 Jun 25.
Germline mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated pituitary adenomas (FIPA). To provide further insight into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and aryl hydrocarbon receptor (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 (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 somatotropinomas and non-secreting PA, and multivariate analysis in somatotropinomas 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 AIPmut PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of non-secreting PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotropinomas. 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.
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