{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T09:43:47Z","timestamp":1769593427998,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Teijin Pharma Limited","award":["Nothing"],"award-info":[{"award-number":["Nothing"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2019 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.<\/jats:p>","DOI":"10.3390\/cancers14030775","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:42:33Z","timestamp":1643866953000},"page":"775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-7122","authenticated-orcid":false,"given":"Hirofumi","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8400-5551","authenticated-orcid":false,"given":"Fumiyoshi","family":"Fujishima","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izumi","family":"Komoto","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kansai Electric Power Hospital, Osaka 553-0003, Japan"},{"name":"Kansai Electric Power Medical Research Institute, Osaka 553-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kansai Electric Power Hospital, Osaka 553-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susumu","family":"Hijioka","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center, Tokyo 104-0045, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya 464-0021, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Yatabe","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Laboratories, National Cancer Center, Tokyo 104-0045, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5301-3847","authenticated-orcid":false,"given":"Atsushi","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 104-0045, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiko","family":"Masui","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Tsuchikawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Pathology, Osaki Citizen Hospital, Osaki 989-6183, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Shiga","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Health Record Informatics, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Nakaya","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyuhiko","family":"Motoi","sequence":"additional","affiliation":[{"name":"Department of Surgery I, Yamagata University Graduate School of Medical Science, Yamagata 990-2331, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiaki","family":"Unno","sequence":"additional","affiliation":[{"name":"Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironobu","family":"Sasano","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000080731","article-title":"Epidemiology of neuroendocrine tumours","volume":"80","author":"Taal","year":"2004","journal-title":"Neuroendocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4251\/wjgo.v12.i8.791","article-title":"Gastrointestinal neuroendocrine tumors in 2020","volume":"12","author":"Ahmed","year":"2020","journal-title":"World J. 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