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

authors

  • Jaffrain-Rea Marie-Lise
  • Rotondi Sandra
  • Turchi Annarita
  • Occhi Gianluca
  • Barlier Anne
  • Peverelli Erika
  • Rostomyan Lilya
  • Defilles Céline
  • Angelini Mariolina
  • Oliva Maria-Antonietta
  • Ceccato Filippo
  • Maiorani Orlando
  • Daly Adrian F
  • Esposito Vincenzo
  • Buttarelli Francesca
  • Figarella-Branger Dominique
  • Giangaspero Felice
  • Spada Anna
  • Scaroni Carla
  • Alesse Edoardo
  • Beckers Albert

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.

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