体•胰腺内分泌肿瘤（pNETs）是一种罕见的胰腺肿瘤，具有高异质性，大多数pNETs通常表达生长抑素受体（somatostatin receptors），然而，生长抑素受体2（SSTR2）在pNET中的作用很少得到单独研究。本回顾性研究旨在评估SSTR2在非功能性和良性分化的pNET的临床病理特征和基因组背景中的作用。共纳入223例非功能性良性分化pNET病例，并评估SSTR2状态与临床病理结果之间的相关性。此外，我们对SSTR2阳性和SSTR2阴性的pNET进行全外显子测序，并发现两种病变具有不同的突变谱。SSTR2免疫组化阴性与疾病早期发生、肿瘤大小增大、进展期美国联合委员会肿瘤阶段、淋巴结和肝转移有显著关联。在病理评估下，SSTR2阴性病例的阳性周边侵袭、血管侵犯和神经周围侵袭显著增加。此外，SSTR2阴性患者的无进展生存显著劣于SSTR2阳性患者(hazard ratio, 0.23; 95% confidence interval, 0.10-0.53; P = 0.001)。生长抑素受体2阴性的非功能性pNET可能代表一种具有不良预后的pNET亚型，并从不同的基因组背景进化而来。Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Somatostatin receptors are commonly expressed in most pancreatic neuroendocrine tumors (pNETs), a rare type of pancreatic tumors with high heterogeneity. However, the role of somatostatin receptor 2 (SSTR2) has seldom been investigated separately in pNET. This retrospective study aims to evaluate the role of SSTR2 in the clinicopathological features and genomic background of nonfunctional and well-differentiated pNET.A total of 223 cases of nonfunctional well-differentiated pNET were included, and the correlation between SSTR2 status and clinicopathological outcome was evaluated. In addition, we performed whole exome sequencing in SSTR2-positive and SSTR2-negative pNETs and identified that the 2 lesions harbored different mutational landscapes.Negative SSTR2 immunochemistry staining was significantly related to an earlier onset of disease, larger tumor size, advanced stage of American Joint Committee on Cancer, and tumor metastasis in lymph nodes and liver. Under pathological assessment, positive peripheral aggression, vascular invasion, and perineural invasion were markedly increased in SSTR2-negative cases. Moreover, SSTR2-negative patients exhibited significantly worse progression-free survival than SSTR2-positive patients (hazard ratio, 0.23; 95% confidence interval, 0.10-0.53; P = 0.001).Somatostatin receptor 2-negative nonfunctional pNET might represent a subtype of pNET with poor outcomes and evolve from a different genomic background.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.