TY - JOUR
T1 - Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations
AU - Jaffrain-Rea, Marie Lise
AU - Rotondi, Sandra
AU - Turchi, Annarita
AU - Occhi, Gianluca
AU - Barlier, Anne
AU - Peverelli, Erika
AU - Rostomyan, Lilya
AU - Defilles, Céline
AU - Angelini, Mariolina
AU - Oliva, Maria Antonietta
AU - Ceccato, Filippo
AU - Maiorani, Orlando
AU - Dal, Adrian F.
AU - Esposito, Vincenzo
AU - Buttarelli, Francesca
AU - Figarella-Branger, Dominique
AU - Giangaspero, Felice
AU - Spada, Anna
AU - Scaroni, Carla
AU - Alesse, Edoardo
AU - Beckers, Albert
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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.
KW - Acromegaly
KW - Aryl hydrocarbon receptor
KW - Gsp mutations
KW - Interacting protein
KW - Pituitary adenoma
KW - Somatostatin analogues
UR - http://www.scopus.com/inward/record.url?scp=84886400400&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84886400400&partnerID=8YFLogxK
U2 - 10.1530/ERC-12-0322
DO - 10.1530/ERC-12-0322
M3 - Article
C2 - 23940012
AN - SCOPUS:84886400400
VL - 20
SP - 753
EP - 766
JO - Endocrine-Related Cancer
JF - Endocrine-Related Cancer
SN - 1351-0088
IS - 5
ER -