title: Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly.
abstract: BACKGROUND
  Somatostatin receptor subtype 2 (sst2A) protein expression has been demonstrated to positively correlate with somatostatin analog treatment outcome in GH-secreting adenomas. Recently, a new rabbit monoclonal anti-sst2A antibody (clone UMB-1) has been validated as a reliable method to selectively detect sst2A protein levels in formalin-fixed tissues.
  
  
  OBJECTIVE
  The aim of the study was to establish whether the evaluation of sst2A protein levels, assessed with a routine reproducible immunohistochemistry protocol using UMB-1 antibody, may predict the successful adjuvant therapy with somatostatin analogs in acromegalic patients.
  
  
  METHODS
  Thirty-six acromegalic patients from our referral hospital were evaluated retrospectively. Sst2A expression analysis was performed by immunohistochemistry in 25 patients and by quantitative RT-PCR in 26 patients. Sst2A immunoreactivity was evaluated using an immunoreactivity score (IRS), which takes into account both the percentage of positive cells and staining intensity.
  
  
  METHODS
  Patients with persistent disease after surgery (n = 26) were treated with somatostatin analogs for a median duration of 6 months.
  
  
  METHODS
  GH and IGF-I levels were measured before and after postoperative treatment.
  
  
  RESULTS
  Sst2A IRS showed a significant positive correlation with both GH (P = 0.039) and IGF-I (P = 0.001) suppression by octreotide. Sst2A IRS was negatively associated with IGF-I levels reached after treatment (P = 0.001), and patients that achieved IGF-I normalization showed significantly higher sst2A IRS compared to the group that was not normalized (P = 0.002). A sst2A IRS of at least 5 showed a sensitivity of 86% and a specificity of 91% in predicting IGF-I normalization during adjuvant octreotide treatment.
  
  
  CONCLUSIONS
  Sst2A IRS with the anti-sst2A antibody UMB-1 represents a valid tool in the clinical practice to identify acromegalic patients likely to be responders to adjuvant therapy with the currently available somatostatin analogs.
authors.affiliation: Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, The Netherlands.
authors.forename: Federico
authors.initials: F
authors.lastname: Gatto
authors.forename: Richard A
authors.initials: RA
authors.lastname: Feelders
authors.forename: Rob
authors.initials: R
authors.lastname: van der Pas
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.forename: Marlijn
authors.initials: M
authors.lastname: Waaijers
authors.forename: Diana
authors.initials: D
authors.lastname: Sprij-Mooij
authors.forename: Sebastian J C M M
authors.initials: SJ
authors.lastname: Neggers
authors.forename: Aart-Jan
authors.initials: AJ
authors.lastname: van der Lelij
authors.forename: Francesco
authors.initials: F
authors.lastname: Minuto
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.forename: Diego
authors.initials: D
authors.lastname: Ferone
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
mesh_terms: D000172:Acromegaly / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D000236:Adenoma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D011379:Prognosis; D011817:Rabbits; D017481:Receptors, Somatostatin / Q000276:immunology*; D012107:Research Design; D012189:Retrospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D018931:Antineoplastic Agents, Hormonal; D054316:Biomarkers, Pharmacological; D017481:Receptors, Somatostatin; C106140:somatostatin receptor sst2A; D013004:Somatostatin; D015282:Octreotide