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

Guido Rindi, Alfredo Pontecorvi, Donato Iacovazzo, Francesca Lugli, Sabrina Chiloiro, Serena Piacentini, Antonio Bianchi, Antonella Giampietro, Marilda Mormando, Francesco Doglietto, Carmelo Anile, Giulio Maira, Libero Lauriola, Laura De Marinis Grasso, Eivind Carlsen, Andrew J. Clear, Federico Roncaroli, Márta Korbonits

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Aim: To gather data regarding factors predicting responsiveness to pasireotide in acromegaly. Patients and methods: SSTR2a, 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. Results: None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to firstgeneration SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (PZ0.04). 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 (PZ0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; PZ0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; PZ0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; PZ0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; PZ0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; PZ0.04). Conclusion: The 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.
Original languageEnglish
Pages (from-to)241-250
Number of pages10
JournalEuropean Journal of Endocrinology
Volume174
DOIs
Publication statusPublished - 2016

Keywords

  • Acromegaly
  • Adenoma
  • Adult
  • Drug Resistance
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Female
  • Growth Hormone-Secreting Pituitary Adenoma
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Ki-67 Antigen
  • Male
  • Middle Aged
  • Receptors, Somatostatin
  • Somatostatin
  • Treatment Outcome

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