title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Endocrine Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional, S.XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
authors.forename: Baldomero
authors.initials: B
authors.lastname: Gonzalez
authors.affiliation: Endocrine Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional, S.XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Vargas
authors.affiliation: Endocrine Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional, S.XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ramirez
authors.affiliation: University Health Network and The Ontario Cancer Center, Toronto, Ontario, Canada.
authors.forename: Silvia
authors.initials: S
authors.lastname: Asa
authors.affiliation: University Health Network and The Ontario Cancer Center, Toronto, Ontario, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Endocrine Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional, S.XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sandoval
authors.affiliation: Endocrine Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional, S.XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico. Electronic address: mmercadoa@yahoo.com.
authors.forename: Moises
authors.initials: M
authors.lastname: Mercado
mesh_terms: D000172:Acromegaly / Q000209:etiology; D000236:Adenoma / Q000737:chemistry* / Q000150:complications / Q000188:drug therapy / Q000601:surgery; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000737:chemistry* / Q000150:complications / Q000188:drug therapy / Q000601:surgery; D019382:Human Growth Hormone / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D015282:Octreotide / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D017481:Receptors, Somatostatin / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C094573:somatostatin receptor 5; D015282:Octreotide
keywords: Acromegalia; Acromegaly; Análogos de la somatostatina; Octreotide; Octreótido; Receptores somatostatinérgicos; Somatostatin analogs; Somatostatin receptors