Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

European Journal of Endocrinology - Tập 174 Số 2 - Trang 241-250 - 2016
Donato Iacovazzo1,2, Eivind Carlsen3, Francesca Lugli2, Sabrina Chiloiro2, Serena Piacentini2, Antonio Bianchi2, Antonella Giampietro2, Marilda Mormando2, Andrew Clear4, Francesco Doglietto5, Carmelo Anile6, Giulio Maira7, Libero Lauriola8, Guido Rindi8, Federico Roncaroli9, Alfredo Pontecorvi2, Márta Korbonits1, Laura De Marinis2
1Endocrinology, Barts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UK
2Endocrinology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
3Pathology, STHF, N-3710 Skien, Norway
4Haemato-Oncology, Barts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UK
5Neurosurgery, Università di Brescia, 25121 Brescia, Italy
6Neurosurgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
7Neurosurgery, Humanitas, 20089 Milan, Italy
8Pathology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
9Brain, Behaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK

Tóm tắt

AimTo gather data regarding factors predicting responsiveness to pasireotide in acromegaly.Patients and methodsSSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0–3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR.ResultsNone of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0–1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0–1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0–1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0–1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04).ConclusionThe expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.

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European Journal of Endocrinology

Tập 174 Số 2

241-250

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