ECE2016 Guided Posters Pituitary - Clinical (10 abstracts)
Impact of AIP and Gαi-2 proteins on clinical features of sporadic GH-secreting pituitary adenomas
Elina Ritvonen 1 , Esa Pitkänen 3 , Atte Karppinen 2 , Satu Vehkavaara 1 , Hande Demir 3 , Anders Paetau 4 , Camilla Schalin-Jäntti 1 & Auli Karhu 3
1Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; 2Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland; 3Department of Medical and Clinical Genetics & Genome-Scale Biology, Research Programs Unit, University of Helsinki, Helsinki, Finland; 4Department of Pathology, HUSLAB, University of Helsinki, Helsinki, Finland.
Introduction: In sporadic acromegaly, downregulation of AIP protein of the adenomas associates with invasive tumour features and reduced response to somatostatin analogue treatment. AIP is a regulator of Gαi signaling, but it is not known how the biological function of the Gαi pathway is controlled.
Aim: To study somatic GNAS and AIP mutation status, AIP and Gαi-2 protein expressions, Ki67 proliferation indices, and clinical parameters in patients having primary surgery because of acromegaly at a single centre between years 2000 and 2010.
Results: Sixty patients (F/M 31/29, mean age 49 (median 50), mean follow-up 7.7 (range 0.6–14.0) years) underwent primary surgery. Of the 60 adenoma specimens, four (6.8%) harboured an AIP and 21 (35%) an activating GNAS (Gsp+) mutation. All adenomas stained positive for Gαi-2, and 55/56 AIP mutation negative adenomas stained positive for AIP protein. Altogether 13/56 (23%) adenomas had low AIP protein levels, and 14/56 (25%) low Gαi-2 staining. A regression model including Gαi-2, Ki 67 proliferation indices and GH (measured 3 months after surgery), best explained the variance in the AIP protein level (P=6.03×10−9). The majority (43%) was explained by Gαi-2 level only. Gsp+ status was not related to AIP or Gαi-2 protein levels, but associated with lower KNOSP grade (P=0.0018, r=0.332), tumours restricted to the sella (P=0.026, r=0.320), and higher preoperative prolactin concentrations (P=0.0017, r=0.032). However, the associations were not significant after correction for multiple testing.
Conclusions: We demonstrate, for the first time, that AIP protein expression associates with Gαi-2 protein intensities in sporadic somatotropinomas. This may indicate a synergetic effect on somatostatin signaling. Low AIP protein levels associate with higher proliferation activity and higher postoperative serum GH, indicating more aggressive adenomas. The AIP mutation rate of 6.8% is fairly high and probably reflects the genetic composition of the Finnish population.
Volume 41
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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