Endocrine Abstracts

Pancreatic neuroendocrine tumors (PNETs) are uncommon neoplasms from the endocrine pancreas, whose incidence is recently rising. Unfortunately, an advanced stage is often found at diagnosis; thus, identification of new molecular diagnostic, prognostic, and therapeutic markers is required. Ghrelin and somatostatin/cortistatin systems are two multifunctional regulatory complexes widely distributed throughout multiple tissues, including the pancreas, where they exert diverse (patho)physiological actions; and alterations in these systems can be associated to development/progression of various cancers. Here, we aim to evaluate expression levels of ghrelin and somatostatin systems components in PNETs and explore their putative relationship with histological/clinical patient features. Namely, an observational retrospective study with 28 PNET patients was performed by collecting clinical/histological characteristics and measuring expression levels of ghrelin and somatostatin/cortistatin systems components, by quantitative-PCR, in formalin-fixed paraffin-embedded PNET samples (n=25; 52.2% G2, 43.5% G1 and 4.3% G3) and in control adjacent non-tumoral tissues. Mean age was 55±14 years (57.1% females); 21.1% of cases were diagnosed incidentally, 42.1% were functioning tumors and 40.7% had metastasis at diagnosis. Tumour diameter associated negatively to vascular invasion (P<0.05) and necrosis (P<0.05). Somatostatin receptor (sst) subtypes-1 and -2, cortistatin and ghrelin O-acil-transferase enzyme were overexpressed in PNETs compared to control-tissues (P<0.01). Presence of skin lesions at diagnosis was correlated to sst3 expression (P<0.05). sst1 expression was negatively associated with vascular invasion (P<0.05). Ghrelin-receptor was negatively associated with nerve invasion (P<0.01). Mortality was associated to metastasis (P<0.05), relapsed disease (P<0.05) and somatostatin expression. Interestingly, there was a trend for mortality and sst3 expression to be associated (P=0.08). Our results indicate that the majority of ghrelin and somatostatin systems components are expressed in PNETs, where some of these components display specific associations with clinical-histological parameters, which may help to better understand PNETs pathophysiology and to identify novel molecular targets with potential prognostic and/or therapeutic value for PNETs patients.