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

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.

• Authors: Federico Gatto, Richard A Feelders, Rob van der Pas, Johan M Kros, Marlijn Waaijers, Diana Sprij-Mooij, Sebastian J C M M Neggers, Aart-Jan van der Lelij, Francesco Minuto, Steven W J Lamberts, Wouter W de Herder, Diego Ferone, Leo J Hofland
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 98 Issue 1 Pg. E66-71 (Jan 2013) ISSN: 1945-7197 [Electronic] United States
• PMID: 23118420 (Publication Type: Evaluation Study, Journal Article, Validation Study)

Chemical References

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

Topics

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