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Somatostatin analogues increase AIP expression in (...)

Endocr Relat Cancer. 2013 Oct ;20(5):753-66
Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations.
Jaffrain Rea ML, Rotondi S, Turchi A, Occhi G, Barlier A, Peverelli E, Rostomyan L, Defilles C, Angelini M, Oliva MA, Ceccato F, Maiorani O, Daly AF, Esposito V, Buttarelli F, Figarella-Branger D, Giangaspero F, Spada A, Scaroni C, Aesse E, Beckers A.

Germline Aryl hydrocarbon receptor Interacting Protein (AIP) gene mutations confer a predisposition to pituitary adenoma (GH), 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 semi-quantitative immunohistochemistry (IHC) scoring in 62 sporadic GH-PA (37 treated with SSA pre-operatively). The influence of Gsp status was studied in a subset of tumours (n=39, 14 Gsp+) and 6 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 2-fold 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 pre-operative 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 pre-operative response, with no clear role for AHR.


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