Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors

SIMPLE SUMMARY: Immunolocalization of somatostatin receptor 2 (SSTR2) could predict the therapeutic efficacy of somatostatin analogues (SSAs) in neuroendocrine tumors (NETs). Therefore, in this study, we evaluated SSTR2 immunoreactivity and elucidated its correlation with clinicopathological variables, including the therapeutic response to SSAs in gastrointestinal neuroendocrine tumors (GI-NETs) using digital image analysis (DIA) and other established methods of evaluation. SSTR2 immunoreactivity in foregut NETs was significantly higher than that in hindgut NETs. SSTR2 immunoreactivity was significantly negatively correlated with the Ki-67 labeling index in foregut NETs but positively correlated in hindgut NETs. Therefore, the significance of SSTR2 immunoreactivity in GI-NETs is considered to be different according to the primary sites. We also first demonstrated that DIA could provide a good alternative for predicting response to SSAs in evaluating SSTR2 immunoreactivity of GI-NETs. ABSTRACT: Somatostatin analogues (SSAs) are widely used to treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Somatostatin receptor 2 (SSTR2) immunoreactivity serves as a predictive marker of the therapeutic efficacy of SSAs in pancreatic NETs. However, SSTR2 expression profiles in tumor cells and their association with the therapeutic efficacy of SSAs remains virtually unknown in gastrointestinal NETs (GI-NETs). Therefore, we evaluated the association between SSTR2 immunoreactivity and embryological origin and proliferative activity in 132 resected surgical tissues of GI-NETs. The correlation between SSAs’ therapeutic efficacy and SSTR2 immunoreactivity was evaluated in 14 GI-NETs treated with SSAs. SSTR2 immunoreactivity was evaluated using Volante scores, immunoreactive scores, and digital image analysis (DIA). SSTR2 immunoreactivity was significantly negatively and positively correlated with the Ki-67 labeling index in foregut and hindgut NETs, respectively. In the normal mucosa, neuroendocrine cells in the rectum had significantly lower positive rates of SSTR2 than those in the stomach and duodenum. SSTR2 expression profiles in GI-NETs could differ by primary sites, while the difference of those between foregut and hindgut NETs might be derived from the SSTR2 status of normal neuroendocrine cell counterparts. In addition, DIA could provide a good alternative for predicting response to SSAs in evaluating SSTR2 immunoreactivity of GI-NETs.