title: Somatostatin receptors in bronchopulmonary neuroendocrine neoplasms: new diagnostic, prognostic, and therapeutic markers.
abstract: OBJECTIVE
  Gastroenteropancreatic neuroendocrine neoplasms are known for their overexpression of somatostatin receptors (SSTRs), which provide the molecular basis for diagnostic and therapeutic interventions. In contrast, few data on the SSTR expression profile exist for bronchopulmonary neuroendocrine neoplasms (BP-NEN).
  
  
  METHODS
  A total of 240 formalin-fixed, paraffin-embedded specimens from 26 typical carcinoid (TC), 30 atypical carcinoid (AC), and 34 small cell lung cancer (SCLC) patients were examined retrospectively by immunohistochemistry (IHC) using specific rabbit monoclonal antibodies and evaluated by the immunoreactive score. Adjacent slides from 20 samples of each tumor type were subjected to additional RT-quantitative PCR mRNA analysis.
  
  
  RESULTS
  With different expression patterns, SSTRs were present in most of the tumor sections, at both the protein and mRNA levels. The RT-quantitative PCR data correlated with the IHC scores. SSTR1 was detected in approximately 65% of the TC and AC, but hardly in the SCLC, whereas both SSTR2A and SSTR5 were present in approximately 45% of each entity. Furthermore, the SSTR1 expression level was positively correlated with patient survival.
  
  
  CONCLUSIONS
  Our results suggest that SSTRs can be used as novel diagnostic, prognostic, and therapeutic markers of BP-NEN. The differences in the SSTR expression profile between the three types of BP-NEN may help to set a diagnostic cutoff and predict patient prognosis. Similar to TC and AC, our results also revealed a previously unappreciated high level of SSTR2A expression in SCLC within a subgroup of patients. However, in most cases, pan-somatostatin analogs may represent an additional therapeutic option.
authors.affiliation: Department of General and Visceral Surgery (D.K.), Zentralklinik Bad Berka, 99437 Bad Berka, Germany; Institute of Pharmacology and Toxicology (E.S., S.S., A.L.), Jena University Hospital, 07747 Jena, Germany; Laboratory of Pathology and Cytology (J.S.), 99437 Bad Berka, Germany; STRATIFYER Molecular Pathology GmbH (R.M.W.), 50935 Cologne, Germany; and Department of Internal Medicine, Gastroenterology, and Endocrinology (M.S.), Zentralklinik Bad Berka, 99437 Bad Berka, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kaemmerer
authors.forename: Elisa
authors.initials: E
authors.lastname: Specht
authors.forename: Jörg
authors.initials: J
authors.lastname: Sänger
authors.forename: Ralph Markus
authors.initials: RM
authors.lastname: Wirtz
authors.forename: Manal
authors.initials: M
authors.lastname: Sayeg
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Amelie
authors.initials: A
authors.lastname: Lupp
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D011379:Prognosis; D017481:Receptors, Somatostatin / Q000502:physiology*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D017481:Receptors, Somatostatin