| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Experimental Medicine, University of L'Aquila, via Vetoio, Coppito 2, 67100 L'Aquila, Italy
2 Neuromed Institute, Istituto di Ricovero e di Ricerca a Carattere Scientifico, Via Atinense 18, 86077 Pozzilli, Italy
3 Fondazione ‘Carlo Ferri’ per la prevenzione e la cura dei tumori, via Edmondo Riva 42, 00015 Monterotondo, Italy
4 Departments of Endocrinology
5 Molecular Genetics, Centre Hospitalier Universitaire de Liège, Université de Liège, 4000 Liège, Belgium
6 Department of Endocrinology, Hôpital de la Timone, Centre de Référence des maladies rares d'origine hypophysaire, Assistance Publique-Hôpitaux de Marseille, and Centre de Recherche en Neurobiologie - Neurophysiologie de Marseille (CRN2M), Unité Mixte de Recherche 6231, Université de la Méditerranée - Université Paul Cézanne - CNRS, 13284 Marseille, France
7 Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza’, Viale dell'Università, 00161 Rome, Italy
8 Pathology, San Salvatore Hospital, Coppito, 67100 L'Aquila, Italy
9 Max Planck Institute of Psychiatry, 80804 Munich, Germany
10 Endocrinology Unit, Faculty of Medicine, University of Brasilia, 70910-900 Brasilia, Brazil
11 Department of Endocrinology, Hospital Universitario de La Ribera, 46600 Alzira, Spain
12 Department of Endocrinology, Sofia University, 1303 Sofia, Bulgaria
13 Endocrinology, Centre Hospitalier Universitaire de Angers, 49033 Angers, France
(Correspondence should be addressed to M-L Jaffrain-Rea; Email: jaffrain.ml{at}libero.it)
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 (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 AIPmut 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.
This article has been cited by other articles:
|
|
 |
|
  E. Heliovaara, A. Raitila, V. Launonen, A. Paetau, J. Arola, H. Lehtonen, T. Sane, R. J. Weil, O. Vierimaa, P. Salmela, et al. The Expression of AIP-Related Molecules in Elucidation of Cellular Pathways in Pituitary Adenomas Am. J. Pathol., December 1, 2009; 175(6): 2501 - 2507. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
