Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations.

Abstract

Germline aryl hydrocarbon receptor interacting protein (AIP) gene mutations confer a predisposition to pituitary adenoma (PA), predominantly GH-secreting (GH-PA). As recent data suggest a role for AIP in the pathogenesis of sporadic GH-PA and their response to somatostatin analogues (SSA), the expression of AIP and its partner, aryl hydrocarbon receptor (AHR), was determined by semiquantitative immunohistochemistry scoring in 62 sporadic GH-PA (37 treated with SSA preoperatively). The influence of Gsp status was studied in a subset of tumours (n=39, 14 Gsp(+)) and six GH-PA were available for primary cultures. AIP and AHR were detected in most cases, with a positive correlation between AIP and cytoplasmic AHR (P=0.012). Low AIP expression was significantly more frequent in untreated vs SSA-treated tumours (44.0 vs 20.5%, P=0.016). AHR expression or localisation did not differ between the two groups. Similarly, in vitro octreotide induced a median twofold increase in AIP expression (range 1.2-13.9, P=0.027) in GH-PA. In SSA-treated tumours, the AIP score was significantly higher in the presence of preoperative IGF1 decrease or tumour shrinkage (P=0.008 and P=0.014 respectively). In untreated tumours, low AIP expression was significantly associated with invasiveness (P=0.028) and suprasellar extension (P=0.019). The only effect of Gsp status was a significantly lower nuclear AHR score in Gsp(+) vs Gsp(-) tumours (P=0.025), irrespective of SSA. In conclusion, AIP is involved in the aggressiveness of sporadic GH-PA, regardless of Gsp status, and AIP up-regulation in SSA-treated tumours is associated with a better preoperative response, with no clear role for AHR.

• Authors: Marie-Lise Jaffrain-Rea, Sandra Rotondi, Annarita Turchi, Gianluca Occhi, Anne Barlier, Erika Peverelli, Lilya Rostomyan, Céline Defilles, Mariolina Angelini, Maria-Antonietta Oliva, Filippo Ceccato, Orlando Maiorani, Adrian F Daly, Vincenzo Esposito, Francesca Buttarelli, Dominique Figarella-Branger, Felice Giangaspero, Anna Spada, Carla Scaroni, Edoardo Alesse, Albert Beckers
• Journal: Endocrine-related cancer (Endocr Relat Cancer) Vol. 20 Issue 5 Pg. 753-66 (Oct 2013) ISSN: 1479-6821 [Electronic] England
• PMID: 23940012 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• GTP-Binding Protein alpha Subunits
• Intracellular Signaling Peptides and Proteins
• Receptors, Aryl Hydrocarbon
• aryl hydrocarbon receptor-interacting protein
• Somatostatin
• Octreotide

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents, Hormonal (pharmacology)
• Female
• GTP-Binding Protein alpha Subunits (genetics)
• Growth Hormone-Secreting Pituitary Adenoma (metabolism)
• Humans
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Male
• Middle Aged
• Mutation
• Octreotide (pharmacology)
• Receptors, Aryl Hydrocarbon (metabolism)
• Somatostatin (analogs & derivatives, pharmacology)
• Young Adult