Cytoplasmic expression of SSTR2 and 5 by immunohistochemistry and by RT/PCR is not associated with the pharmacological response to octreotide.

Abstract

OBJECTIVE:

To evaluate expression of somatostatin receptor subtypes 2 and 5 (SSTR 2 and 5) by RT/PCR and immunohistochemistry (IHC) in GH-secreting adenomas, seeking correlations with response to octreotide.

METHODS:

SSTR2 and 5 expression was tested by IHC (n=37), RT/PCR (n=36) or both (n=13) in GH-secreting adenomas from 60 patients with acromegaly who had undergone pituitary surgery; 36 had been treated preoperatively with octreotide LAR for 3-6 months, and were categorized as responders (achievement of GH <2.5ng/mL and a normal age-adjusted IGF-1), partial responders (GH and IGF-1 reduction >50% and >30%, respectively) or non-responders. IHC was performed on a tissue microarray using specific antibodies directed to the carboxyl terminus of SSTR2 and 5.

RESULTS:

SSTR5 was the predominantly expressed receptor subtype by both IHC and RT/PCR in all tumors tested, regardless of whether they came from octreotide-naïve, octreotide-responsive, or octreotide-resistant patients. Immunostaining was concentrated in the cytoplasm. Neither SSTR2 nor SSTR5 expression correlated with baseline or post-octreotide GH or IGF-1 levels or tumor volume by either method. The agreement rate between RT/PCR and IHC was 77% in all 13 adenomas in which both methods were used.

CONCLUSION:

Expression of these receptors does not guarantee an adequate response to somatostatin analogs; other functional aspects of this interaction, such as receptor homo- and heterodimerization, and the resulting signaling cascade, probably play a role in determining whether a patient will respond or not to these agents.

• Authors: Baldomero Gonzalez, Guadalupe Vargas, Claudia Ramirez, Silvia Asa, Sonia Cheng, Carolina Sandoval, Moises Mercado
• Journal: Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion (Endocrinol Nutr) Vol. 61 Issue 10 Pg. 523-30 (Dec 2014) ISSN: 1579-2021 [Electronic] Spain
• PMID: 25008035 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

Chemical References

• Antineoplastic Agents, Hormonal
• Neoplasm Proteins
• Receptors, Somatostatin
• SSTR2 protein, human
• Human Growth Hormone
• Insulin-Like Growth Factor I
• somatostatin receptor 5
• Octreotide

Topics

• Acromegaly (etiology)
• Adenoma (chemistry, complications, drug therapy, surgery)
• Antineoplastic Agents, Hormonal (therapeutic use)
• Combined Modality Therapy
• Drug Resistance, Neoplasm
• Gene Expression Regulation, Neoplastic
• Growth Hormone-Secreting Pituitary Adenoma (chemistry, complications, drug therapy, surgery)
• Human Growth Hormone (analysis, metabolism)
• Humans
• Hypophysectomy
• Insulin-Like Growth Factor I (analysis)
• Neoplasm Proteins (biosynthesis, genetics)
• Octreotide (therapeutic use)
• Real-Time Polymerase Chain Reaction
• Receptors, Somatostatin (biosynthesis, genetics)
• Tissue Array Analysis