Watanabe Hirofumi, Fujishima Fumiyoshi, Yamazaki Yuto, Imamura Masayuki, Hijioka Susumu, Hara Kazuo, Kuwahara Takamichi, Yatabe Yasushi, Sakamoto Kazuhiro, Shiga Hisashi, Kawaguchi Tomohiro, Suzuki Hiroyoshi, Kanbayashi Yumi, Ohkoshi Akira, Shimada Muneaki, Niikawa Hiromichi, Sato Mami, Fujio Atsushi, Masui Toshihiko, Kasai Yosuke, Ota Hideki, Ozawa Hiroshi, Endo Hidenori, Unno Michiaki, Sasano Hironobu, Suzuki Takashi
Department of Pathology, Tohoku University Hospital, 1 - 1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980 - 8574, Japan.
Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan.
Virchows Arch. 2025 Apr 26. doi: 10.1007/s00428-025-04098-2.
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, and both negative cases as Ins. 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, Ins, 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 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.
放射性标记的胰高血糖素样肽1（GLP-1）类似物闪烁扫描术是一种用于检测小胰岛素瘤的新型高灵敏度成像方法。生长抑素受体闪烁扫描术（SRS）是一种用于检测胃肠胰神经内分泌肿瘤的成熟方法。然而，使用SRS很难检测出小的良性胰岛素瘤。此外，GLP-1受体（GLP-1R）表达与SRS结果可能呈负相关。我们鉴定了689例神经内分泌肿瘤，包括胰腺神经内分泌肿瘤（PanNETs）和起源于非胰腺部位的神经内分泌肿瘤，并进行了GLP-1R免疫染色。在非胰岛素瘤性PanNETs中，免疫组化胰岛素或胰岛素原阳性病例归类为Ins，两者均为阴性的病例归类为Ins。在PanNETs和十二指肠神经内分泌肿瘤中检测到GLP-1R表达的高患病率（分别为34%和53%）。一些肺神经内分泌肿瘤为GLP-1R阳性（9%）。相比之下，除1例病例外的胃肠道神经内分泌癌和肺神经内分泌癌均未表现出GLP-1R表达。Ins、Ins和胰岛素瘤的GLP-1R阳性病例百分比分别为31%、0%和84%。在PanNETs中，GLP-1R阳性病例的胰岛素和胰岛素原表达高于阴性病例。SRS阳性患者的胰岛素、胰岛素原和GLP-1R表达水平低于SRS阴性患者。PanNETs和十二指肠神经内分泌肿瘤中的表达可能源于其正常对应物中的表达。胰岛素瘤和Ins病例表现出GLP-1R表达。此外，由于GLP-1R阳性患者的胰岛素和胰岛素原表达明显高于GLP-1R阴性患者，GLP-1R也可能与肿瘤性胰岛素产生相关，并且GLP-1类似物闪烁扫描术可能检测到亚临床胰岛素瘤。此外，SRS阴性病例的GLP-1R表达明显高于SRS阳性病例。这些结果表明GLP-1类似物闪烁扫描术与SRS联合作为检测工具的应用潜力。
