Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations.
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.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy. marielise.jaffrain@univaq.it
Marie-Lise
ML
Jaffrain-Rea
Sandra
S
Rotondi
Annarita
A
Turchi
Gianluca
G
Occhi
Anne
A
Barlier
Erika
E
Peverelli
Lilya
L
Rostomyan
Céline
C
Defilles
Mariolina
M
Angelini
Maria-Antonietta
MA
Oliva
Filippo
F
Ceccato
Orlando
O
Maiorani
Adrian F
AF
Daly
Vincenzo
V
Esposito
Francesca
F
Buttarelli
Dominique
D
Figarella-Branger
Felice
F
Giangaspero
Anna
A
Spada
Carla
C
Scaroni
Edoardo
E
Alesse
Albert
A
Beckers
D000293:Adolescent; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015282:Octreotide / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D055815:Young Adult
D018931:Antineoplastic Agents, Hormonal; D044385:GTP-Binding Protein alpha Subunits; D047908:Intracellular Signaling Peptides and Proteins; D018336:Receptors, Aryl Hydrocarbon; C103265:aryl hydrocarbon receptor-interacting protein; D013004:Somatostatin; D015282:Octreotide
Gsp mutations; acromegaly; aryl hydrocarbon receptor; aryl hydrocarbon receptor interacting protein; pituitary adenoma; somatostatin analogues