Somatostatin receptors in bronchopulmonary neuroendocrine neoplasms: new diagnostic, prognostic, and therapeutic markers

J Clin Endocrinol Metab. 2015 Mar;100(3):831-40. doi: 10.1210/jc.2014-2699. Epub 2014 Dec 12.


Context and objectives: 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).

Design and settings: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / genetics
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / therapy*
  • Prognosis
  • Receptors, Somatostatin / physiology*
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Treatment Outcome


  • Biomarkers, Tumor
  • Receptors, Somatostatin