title: Expression of Somatostatin Receptors 1-5 and Dopamine Receptor 2 in Lung Carcinoids: Implications for a Therapeutic Role.
abstract: OBJECTIVE
  The expression of somatostatin receptors (SSTRs) and dopamine receptor 2 (DR2) in neuroendocrine tumors is of clinical importance as somatostatin analogues and dopamine agonists can be used for their localization and/or treatment. The objective of this study is to examine the expression of the five SSTR subtypes and DR2 in lung carcinoids (LCs).
  
  
  METHODS
  We conducted a retrospective study of 119 LCs from 106 patients [typical carcinoids (TCs): n = 100, and atypical carcinoids (ACs): n = 19]. The expression of all five SSTR subtypes and DR2 was evaluated immunohistochemically and correlated to clinicopathological data. In a subgroup of cases, receptor expression was further analyzed using semiquantitative RT-PCR.
  
  
  RESULTS
  SSTR2A was the SSTR subtype most frequently expressed immunohistochemically (72%), followed by SSTR1 (63%), SSTR5 (40%), and SSTR3 (20%), whereas SSTR4 was negative. DR2 was expressed in 74% and co-expressed with SSTR1 in 56%, with SSTR2A in 59%, with SSTR3 in 19%, and with SSTR5 in 37% of the tumors. Receptor expression was not related to the histological subtype, tumor aggressiveness (disease extent/grading) or functionality; however, DR2 was expressed more frequently in ACs than TCs (95 vs. 70%, p = 0.017). In a subset of patients, RT-PCR findings highly suggested that the expression of SSTR2A, SSTR3, DR2, and to a lesser extent that of SSTR1 and SSTR5 is the outcome of increased gene transcription.
  
  
  CONCLUSIONS
  The high and variable immunohistochemical expression of the majority of SSTRs along with their co-expression with DR2 in LCs provides a rationale for their possible treatment with agents that target these receptors.
authors.affiliation: Endocrine Unit, Department of Pathophysiology, University of Athens Medical School, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Kanakis
authors.forename: Lars
authors.initials: L
authors.lastname: Grimelius
authors.forename: Athanasios
authors.initials: A
authors.lastname: Spathis
authors.forename: Rodoula
authors.initials: R
authors.lastname: Tringidou
authors.forename: George Z
authors.initials: GZ
authors.lastname: Rassidakis
authors.forename: Kjell
authors.initials: K
authors.lastname: Öberg
authors.forename: Gregory
authors.initials: G
authors.lastname: Kaltsas
authors.forename: Apostolos V
authors.initials: AV
authors.lastname: Tsolakis
mesh_terms: D002276:Carcinoid Tumor / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D009363:Neoplasm Proteins; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; C103631:somatostatin receptor 3; C098681:somatostatin receptor subtype-4; C101130:somatostatin receptor type 1; C094573:somatostatin receptor 5