title: Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study.
abstract: OBJECTIVE
  To gather data regarding factors predicting responsiveness to pasireotide in acromegaly.
  
  
  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 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Donato
authors.initials: D
authors.lastname: Iacovazzo
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Eivind
authors.initials: E
authors.lastname: Carlsen
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lugli
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Chiloiro
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Serena
authors.initials: S
authors.lastname: Piacentini
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Antonella
authors.initials: A
authors.lastname: Giampietro
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Marilda
authors.initials: M
authors.lastname: Mormando
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Clear
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Doglietto
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Anile
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Giulio
authors.initials: G
authors.lastname: Maira
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Guido
authors.initials: G
authors.lastname: Rindi
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Federico
authors.initials: F
authors.lastname: Roncaroli
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK m.korbonits@qmul.ac.uk.
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
authors.affiliation: EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK.
authors.forename: Laura
authors.initials: L
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mesh_terms: D000172:Acromegaly / Q000188:drug therapy*; D000236:Adenoma / Q000188:drug therapy*; D000328:Adult; D004351:Drug Resistance; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; C103265:aryl hydrocarbon receptor-interacting protein; C103631:somatostatin receptor 3; D013004:Somatostatin; C094573:somatostatin receptor 5; C517782:pasireotide