ICEECE2012 Poster Presentations Pituitary Basic (30 abstracts)
Aryl hydrocarbon receptor interacting protein in somatotroph adenomas: a molecular target for somatostatin analogues?
M. Jaffrain-Rea 1, , M. Angelini 1 , G. Occhi 3 , A. Turchi 1 , E. Castermans 4 , F. Ceccato 3 , A. Arcella 2 , V. Esposito 2 , F. Giangaspero 2 , G. Pennelli 3 , A. Daly 4 , E. Alesse 1 , C. Scaroni 3 & A. Beckers 4
1University of L’Aquila, L’Aquila, Italy; 2Neuromed Institute, IRCCS, Pozzilli, Italy; 3University of Padova, Padova, Italy; 4CHU, University of Liège, Liège, Belgium.
The aryl hydrocarbon receptor interacting protein (AIP) gene is abundantly expressed in normal somatotrophs. Somatotropinomas in patients with germline AIP mutations (AIPmut) are typically more aggressive than non-AIPmut adenomas and associated with higher GH/IGF1 secretion. AIP downregulation may also occur in sporadic somatotropinomas, especially in invasive tumours. We wished to evaluate the impact of somatostatin analogues (SSA) pre-treatment on AIP expression in sporadic somatotropinomas.
Patients and methods: 46 sporadic somatotropinomas have been operated on in 44 Italian patients, including 20 cases treated by SSA pre-operatively. Pre-operative clinical, radiological and hormonal data were collected. AIP sequencing was performed in most cases and AIP expression was determined by immunohistochemistry (AIP–IHC). χ2 and non-parametric tests were used for statistical analysis.
Results: A single AIP mutation was identified and 17 macroadenomas displayed a faint or negative AIP staining (36.9%). Low AIP–IHC was significantly associated with the presence of suprasellar extension (P=0.003), cavernous sinus invasion (P=0.024), higher MIB1 proliferation indexes (P=0.026), with a trend in higher pre-operative GH levels (P=0.066) and no significant difference in PRL/IGF1 levels. Pre-operative SSA treatment was associated with a significantly higher AIP expression, only three pre-treated adenomas displaying low AIP–IHC (15 vs 53.6% in untreated cases, P=0.007): all were male GH/PRL-secreting adenomas, poorly responsive to SSA, including the AIPmut case. Introducing SSA pre-treatment as a covariant in statistical analysis, low AIP was confirmed to be associated with tumour characteristics but not with GH secretion. Significant correlations between tumour characteristics and AIP–IHC were also confirmed in untreated tumours taken as a subgroup, but not in treated tumours.
Conclusion: While confirming that AIP downregulation is associated with tumour aggressiveness in sporadic somatropinomas, regardless of AIP mutations, these data also suggest a role for AIP in SSA signalling in these tumors. This could contribute to the frequent pharmacological resistance of AIPmut somatotropinomas.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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