Abstract
Simple SummaryImmunolocalization 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.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.
Highlights
The incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has recently increased, possibly because of an increased administration of proton pump inhibitors and developments in detection equipment such as endoscopy [1,2,3]
The Correlations of Somatostatin receptor 2 (SSTR2) Immunoreactivity Evaluated by Three Scoring Systems
Significant correlations were detected between the SSTR2 immunoreactivity evaluated using all three scoring systems
Summary
The incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has recently increased, possibly because of an increased administration of proton pump inhibitors and developments in detection equipment such as endoscopy [1,2,3]. GI-NETs are both clinically and pathologically heterogeneous tumors [7,8,9]. This heterogeneity is pronounced in their endocrine activities and tumor growth, possibly because GI-NETs originate from a variety of neuroendocrine cells located in different sites [10]. Somatostatin, a peptide hormone that binds to the SSTR, has been reported to be expressed in many parts of the body, including the pituitary glands, pancreas, and gastrointestinal tract [12,13,14]. Somatostatin analogues (SSAs), including octreotide and lanreotide, have been widely used as therapeutic agents in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) due to their anti-secretory and/or anti-proliferative activities [9,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
