Endocrine Abstracts

Neuroendocrine tumors (NETs) are uncommon neoplasms with increasing incidence and limited therapeutic options, wherein identification of new diagnostic/prognostic/therapeutic biomarkers is urgently required. Alterations in somatostatin (SST)/cortistatin (CORT) and ghrelin systems have been associated to development/progression of several cancers. Thus, we evaluated expression levels of SST/CORT/ghrelin system components in gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) and lung carcinoids (LC), and explored their putative relationship with clinical/histological characteristics in an observational retrospective study with 90 GEP-NET patients (51.7%-G1, 36.7%-G2, 11.7%-G3), 81 LC patients and 20 controls. Clinical/histological characteristics of GEP-NET and LC patients were, respectively: mean age 54±17/54±15 years; 53.3%/50.6% males; 37.7%/19.2% incidental tumors; 34.4%/7.5% functioning tumors; 46.5%–25% metastatic at diagnosis; and 34.1%–19.4% mortality rate. Expression levels of SST/CORT/ghrelin systems components were assessed by quantitative-PCR using formalin-fixed paraffin-embedded samples. Results indicated that mortality in GEP-NETs patients correlated with metastasis, SST immunostaining, and relapsed disease, and tended to correlate with vascular/nerve invasion. Similarly, in LC patients, mortality was related with relapsed disease and metastasis, but also with tumor diameter, gender, tobacco exposure, weight loss, and constitutional syndrome. Quantitative-PCR studies revealed that the vast majority of SST/CORT/ghrelin systems components were expressed in GEP-NETs and LCs and displayed clinical correlates. Thus, for example, SST, CORT and receptor sst4 expression was lower in GEP-NETs from patients without family tumor history. Interestingly, sst2 and sst3 expression was correlated with tumor-free surgical borders, while sst5 expression correlated with vascular and nerve invasion. Additionally, truncated sst5TMD4 expression was higher in functioning/symptomatic, and metastatic tumors. In LCs, ghrelin expression was inversely associated with vascular invasion and with recurrence, while expression of its receptor GHSR1a was higher in non-functioning and metastatic tumors. Altogether, these data reveals a notable, widespread expression of key SST/CORT/ghrelin systems components in GEP-NETs and LC, where they display clinical-histological correlates, which could provide novel, valuable markers for NET patient management.