GLP- 1R status using validated monoclonal antibody in 689 cases of neuroendocrine neoplasm and its correlation with somatostatin receptor scintigraphy, insulin production, and histological grades

Radiolabeled glucagon-like peptide 1 (GLP- 1) analog scintigraphy is a new, high-sensitivity imaging method for detecting small insulinomas. Somatostatin receptor scintigraphy (SRS) is an established method for detecting gastroenteropancreatic neuroendocrine tumors. However, small benign insulinomas are difficult to detect using SRS. Furthermore, GLP- 1 receptor (GLP- 1R) expression and SRS results may be inversely correlated. We identified 689 neuroendocrine neoplasms, including pancreatic neuroendocrine tumors (PanNETs) and neuroendocrine neoplasms originating from non-pancreatic sites, and performed GLP- 1R immunostaining. Among the non-insulinoma PanNETs, immunohistochemical insulin or proinsulin positive cases were categorized as Ins<sub>pos</sub>, and both negative cases as Ins<sub>neg</sub>. High prevalence of GLP- 1R expression was detected in PanNETs and duodenal NETs (34% and 53%, respectively). Some pulmonary NETs were GLP- 1R positive (9%). In contrast, neither GI-NEC excluding one case nor pulmonary NEC exhibited GLP- 1R expression. The percentage of GLP- 1R positive cases for Ins<sub>pos</sub>, Ins<sub>neg</sub>, and insulinoma was 31%, 0%, and 84%, respectively. Among PanNETs, GLP- 1R positive cases showed higher expression of insulin and proinsulin than negative cases. SRS-positive patients showed lower expression levels of insulin, proinsulin, and GLP- 1R than SRS-negative patients. The expression in PanNETs and duodenal NETs may be derived from the expression in their normal counterparts. Insulinoma and Ins<sub>pos</sub> cases showed GLP- 1R expression. Furthermore, as GLP- 1R-positive patients showed significantly higher expression of insulin and proinsulin than GLP- 1R negative patients, GLP- 1R may also be associated with neoplastic insulin production and GLP- 1 analog scintigraphy may detect subclinical insulinomas. In addition, SRS-negative cases showed significantly higher GLP- 1R expression than SRS-positive cases. These results suggest the application potential of GLP- 1 analog scintigraphy in combination with SRS as a detection tool.

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Journal
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
Published
2025-04-26
DOI
https://doi.org/10.1007/s00428-025-04098-2
Citations
2
Primary Topic
Neuroendocrine Tumor Research Advances
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article
Field-Weighted Citation Impact
2.71
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article

GLP- 1R status using validated monoclonal antibody in 689 cases of neuroendocrine neoplasm and its correlation with somatostatin receptor scintigraphy, insulin production, and histological grades

Hideki Ota, Akira Ohkoshi, Muneaki Shimada, Hiroshi Ozawa et al.
2 citations
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
Neuroendocrine Tumor Research Advances
2.71
article

GLP- 1R status using validated monoclonal antibody in 689 cases of neuroendocrine neoplasm and its correlation with somatostatin receptor scintigraphy, insulin production, and histological grades

Hideki Ota, Akira Ohkoshi, Muneaki Shimada, Hiroshi Ozawa, Hironobu Sasano, Fumiyoshi Fujishima, Kazuhiro Sakamoto, Kazuo Hara, Takashi Suzuki, Yuto Yamazaki, Yosuke Kasai, Hidenori Endo, Yasushi Yatabe, Takamichi Kuwahara, Toshihiko Masui, Hisashi Shiga, Atsushi Fujio, Hiromichi Niikawa, Tomohiro Kawaguchi, Hirofumi Watanabe, Michiaki Unno, Susumu Hijioka, Mami Sato, Hiroyoshi Suzuki, Masayuki Imamura, Yumi Kanbayashi
article en
2 citations

Abstract

Radiolabeled glucagon-like peptide 1 (GLP- 1) analog scintigraphy is a new, high-sensitivity imaging method for detecting small insulinomas. Somatostatin receptor scintigraphy (SRS) is an established method for detecting gastroenteropancreatic neuroendocrine tumors. However, small benign insulinomas are difficult to detect using SRS. Furthermore, GLP- 1 receptor (GLP- 1R) expression and SRS results may be inversely correlated. We identified 689 neuroendocrine neoplasms, including pancreatic neuroendocrine tumors (PanNETs) and neuroendocrine neoplasms originating from non-pancreatic sites, and performed GLP- 1R immunostaining. Among the non-insulinoma PanNETs, immunohistochemical insulin or proinsulin positive cases were categorized as Ins<sub>pos</sub>, and both negative cases as Ins<sub>neg</sub>. High prevalence of GLP- 1R expression was detected in PanNETs and duodenal NETs (34% and 53%, respectively). Some pulmonary NETs were GLP- 1R positive (9%). In contrast, neither GI-NEC excluding one case nor pulmonary NEC exhibited GLP- 1R expression. The percentage of GLP- 1R positive cases for Ins<sub>pos</sub>, Ins<sub>neg</sub>, and insulinoma was 31%, 0%, and 84%, respectively. Among PanNETs, GLP- 1R positive cases showed higher expression of insulin and proinsulin than negative cases. SRS-positive patients showed lower expression levels of insulin, proinsulin, and GLP- 1R than SRS-negative patients. The expression in PanNETs and duodenal NETs may be derived from the expression in their normal counterparts. Insulinoma and Ins<sub>pos</sub> cases showed GLP- 1R expression. Furthermore, as GLP- 1R-positive patients showed significantly higher expression of insulin and proinsulin than GLP- 1R negative patients, GLP- 1R may also be associated with neoplastic insulin production and GLP- 1 analog scintigraphy may detect subclinical insulinomas. In addition, SRS-negative cases showed significantly higher GLP- 1R expression than SRS-positive cases. These results suggest the application potential of GLP- 1 analog scintigraphy in combination with SRS as a detection tool.

Archiv für Pathologische Anatomie und Physiologie und für Klinische MedicinVol. 486(6)
Tohoku University (JP), Kyoto University (JP), Tohoku University Hospital (JP), Osaki Citizen Hospital (JP), Kansai Electric Power Hospital (JP), Aichi Cancer Center (JP), Tohoku Medical and Pharmaceutical University Hospital (JP), Kohnan Hospital (JP), Tochigi Medical Center (JP), Tohoku Medical and Pharmaceutical University (JP)
Good health and well-being
Openalex Percentile: Top 11%
Neuroendocrine Tumor Research Advances
2.71
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