Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly

J Clin Endocrinol Metab. 2013 Jan;98(1):E66-71. doi: 10.1210/jc.2012-2609. Epub 2012 Nov 1.

Abstract

Context: 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.

Design, setting, and patients: 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.

Interventions: Patients with persistent disease after surgery (n = 26) were treated with somatostatin analogs for a median duration of 6 months.

Main outcome measure: 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.

Conclusion: 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.

Publication types

  • Evaluation Study
  • Validation Study

MeSH terms

  • Acromegaly / diagnosis*
  • Acromegaly / drug therapy*
  • Acromegaly / metabolism
  • Adenoma / diagnosis
  • Adenoma / drug therapy
  • Adenoma / metabolism
  • Adult
  • Aged
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers, Pharmacological / analysis
  • Biomarkers, Pharmacological / metabolism
  • Chemotherapy, Adjuvant
  • Female
  • Growth Hormone-Secreting Pituitary Adenoma / diagnosis
  • Growth Hormone-Secreting Pituitary Adenoma / drug therapy
  • Growth Hormone-Secreting Pituitary Adenoma / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Octreotide / therapeutic use*
  • Prognosis
  • Rabbits
  • Receptors, Somatostatin / immunology*
  • Research Design
  • Retrospective Studies
  • Somatostatin / analogs & derivatives*
  • Somatostatin / therapeutic use
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Pharmacological
  • Receptors, Somatostatin
  • somatostatin receptor sst2A
  • Somatostatin
  • Octreotide