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Cytoplasmic expression of SSTR2 and 5 by immunohistochemistry and by RT/PCR is not associated with the pharmacological response to octreotide
Affiliation:1. Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), and Hospital Universitario Reina Sofia.;2. CIBER Fisiopatología de la Obesidad y Nutrición;3. Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014, Córdoba, Spain;4. Endocrinology Unit, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;5. Endocrinology Section, Federal Hospital of Lagoa, Rio de Janeiro, Brazil;6. Endocrinology Section, Hospital Universitario Antônio Pedro, Universidade Federal Fluminense, Rio de Janeiro, Brazil;7. Metabolism and Nutrition Unit, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, Seville 41013, Spain;8. Endocrinology and Nutrition Unit, Complejo Hospitalario de Jaén, Jaén 23007, Spain;9. Service of Endocrinology and Nutrition, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofia, Córdoba 14004, Spain;10. Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Research and Development Division, University of Illinois at Chicago, Chicago, IL, USA;11. IPSEN Bioscience, Cambridge, MA 02142, USA
Abstract:ObjectiveTo 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.MethodsSSTR2 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 <2.5 ng/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.ResultsSSTR5 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.ConclusionExpression 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.
Keywords:Acromegaly  Somatostatin receptors  Octreotide  Somatostatin analogs  Acromegalia  Receptores somatostatinérgicos  Octreótido  Análogos de la somatostatina
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