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

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. Dal, Vincenzo Esposito, Francesca Buttarelli, Dominique Figarella-Branger, Felice Giangaspero, Anna Spada, Carla Scaroni, Edoardo AlesseAlbert Beckers

Research output: Contribution to journalArticlepeer-review

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 treatedwith SSA preoperatively). The influence of Gsp statuswas studied in a subset of tumours (nZ39, 14 GspC) 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 (PZ0.012). Low AIP expression was significantly more frequent in untreated vs SSA-treated tumours (44.0 vs 20.5%, PZ0.016). 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, PZ0.027) in GH-PA. In SSA-treated tumours, the AIP score was significantly higher in the presence of preoperative IGF1 decrease or tumour shrinkage (PZ0.008 and PZ0.014 respectively). In untreated tumours, low AIP expression was significantly associated with invasiveness (PZ0.028) and suprasellar extension (PZ0.019). The only effect of Gsp status was a significantly lower nuclear AHR score in GspC vs GspK tumours (PZ0.025), 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.

Original languageEnglish
Pages (from-to)753-766
Number of pages14
JournalEndocrine-Related Cancer
Volume20
Issue number5
DOIs
Publication statusPublished - Oct 2013

Keywords

  • Acromegaly
  • Aryl hydrocarbon receptor
  • Gsp mutations
  • Interacting protein
  • Pituitary adenoma
  • Somatostatin analogues

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

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