Watanabe Hirofumi, Fujishima Fumiyoshi, Unno Michiaki, Sasano Hironobu, Suzuki Takashi
Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan.
Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan.
Pathol Res Pract. 2023 Apr;244:154418. doi: 10.1016/j.prp.2023.154418. Epub 2023 Mar 18.
Somatostatin is known to inhibit the secretion of various hormones by acting on endocrine cells through the somatostatin receptor 2 (SSTR2). Immunohistochemical evaluation of SSTR2 has become increasingly important in clinical practice to determine treatment strategies for patients with a neuroendocrine tumor (NET). Gastrointestinal (GI) tracts contain various neuroendocrine cells that constitute a diffuse endocrine system and some NETs are derived from those cells. In addition, NETs have been well known to express a variable spectrum of proteins shared by their normal cell counterparts of the specific anatomical sites. Thus, we may derive the kinetics of SSTR2 expression of NETs, including de novo expression, from the SSTR2 expression of the corresponding normal neuroendocrine cells. Therefore, a detailed study on the distribution of SSTR2 in normal human neuroendocrine cells may contribute to understanding the expression of SSTR2 in GI-NETs. However, the detailed cellular localization of SSTR2 in non-neoplastic neuroendocrine cells remains unknown. Therefore, we immunolocalized SSTR2 in neuroendocrine cells of normal human GI tracts, including the stomach, duodenum, ileum, and rectum, obtained from 41 surgically resected tissue specimens. Double immunohistochemistry of SSTR2 and hormones or hormone-associated proteins was performed. In all GI neuroendocrine cells, cell types other than D- and EC-cells demonstrated a high percentage of SSTR2-positive cases or a high double-positive ratio. In particular, EC-cells showed lower SSTR2-positive ratios in all sites. Midgut NETs, which often produce serotonin, are excellent targets for somatostatin analogs and are positive for SSTR2. Thus, we speculated that EC-cell NETs might lead to the de novo expression of SSTR2. In addition, a previous report showed high SSTR2 expression in ECL-cell NETs and gastrinomas, which could be because they are derived from neuroendocrine cells with high SSTR2 expression. This study may contribute to understanding the expression of SSTR2 in GI-NETs.
已知生长抑素通过生长抑素受体2（SSTR2）作用于内分泌细胞，从而抑制各种激素的分泌。在临床实践中，对SSTR2进行免疫组织化学评估对于确定神经内分泌肿瘤（NET）患者的治疗策略变得越来越重要。胃肠道包含构成弥散内分泌系统的各种神经内分泌细胞，一些NETs就源自这些细胞。此外，众所周知，NETs表达其特定解剖部位正常细胞对应物所共有的多种蛋白质。因此，我们可以从相应正常神经内分泌细胞的SSTR2表达情况推导出NETs中SSTR2表达的动力学，包括从头表达。因此，对正常人类神经内分泌细胞中SSTR2分布的详细研究可能有助于理解胃肠道神经内分泌肿瘤（GI-NETs）中SSTR2的表达。然而，SSTR2在非肿瘤性神经内分泌细胞中的详细细胞定位仍然未知。因此，我们对从41例手术切除的组织标本中获取的正常人类胃肠道神经内分泌细胞（包括胃、十二指肠、回肠和直肠）进行了SSTR2免疫定位。进行了SSTR2与激素或激素相关蛋白的双重免疫组织化学检测。在所有胃肠道神经内分泌细胞中，除D细胞和EC细胞外的其他细胞类型显示出高比例的SSTR阳性病例或高双重阳性率。特别是，EC细胞在所有部位的SSTR2阳性率较低。经常产生5-羟色胺的中肠NETs是生长抑素类似物的理想靶点，且SSTR2呈阳性。因此，我们推测EC细胞NETs可能导致SSTR2的从头表达。此外，先前的一份报告显示，ECL细胞NETs和胃泌素瘤中SSTR2表达较高，这可能是因为它们源自具有高SSTR2表达的神经内分泌细胞。本研究可能有助于理解胃肠道神经内分泌肿瘤中SSTR2的表达。
Zotero 插件