Department of Pathology, HUSLAB, HUS Diagnostic Center, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland.
Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00290 Helsinki, Finland.
Int J Mol Sci. 2023 Oct 13;24(20):15164. doi: 10.3390/ijms242015164.
Insulinomas are rare functional pancreatic neuroendocrine tumours, which metastasize in 10% of cases. As predicting the prognosis can be challenging, there is a need for the determination of clinicopathological factors associated with metastatic potential. The aim of this study is to evaluate the glucagon-like peptide-1 receptor (GLP-1R) expression in insulinomas and to analyse its association with clinicopathological features and patient outcome. This retrospective study involves pancreatic tumour tissue samples from fifty-two insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with a monoclonal GLP-1R antibody. Forty-eight of the forty-nine (98%) non-metastatic tumours expressed GLP-1R, while one non-metastatic, multiple endocrine neoplasia type 1 (MEN1)-related tumour and all three of the metastatic tumours lacked GLP-1R expression. The lack of GLP-1R expression was associated with impaired overall survival, larger tumour diameter, higher Ki-67 PI and weaker insulin staining. Somatostatin receptor 1-5 expression did not differ between GLP-1R-positive and GLP-1R-negative insulinomas. In conclusion, the lack of GLP-1R expression is associated with metastatic disease and impaired survival in insulinoma patients. Thus, GLP-1R expression could be a useful biomarker in estimating the metastatic potential of the tumour and the prognosis of surgically treated patients.
胰岛素瘤是罕见的功能性胰腺神经内分泌肿瘤,约有 10%的病例发生转移。由于预测预后具有挑战性,因此需要确定与转移潜能相关的临床病理因素。本研究旨在评估胰岛素瘤中胰高血糖素样肽-1 受体 (GLP-1R) 的表达,并分析其与临床病理特征和患者预后的关系。本回顾性研究纳入了 52 例胰岛素瘤患者的胰腺肿瘤组织样本。经过组织学重新评估后,使用抗 GLP-1R 单克隆抗体对福尔马林固定石蜡包埋组织样本进行免疫组织化学染色,并制作组织微阵列。49 例非转移性肿瘤中有 48 例(98%)表达 GLP-1R,而 1 例非转移性、多发性内分泌肿瘤 1 型 (MEN1) 相关肿瘤和 3 例转移性肿瘤均不表达 GLP-1R。GLP-1R 表达缺失与总生存期缩短、肿瘤直径较大、Ki-67 PI 较高和胰岛素染色较弱有关。GLP-1R 阳性和 GLP-1R 阴性胰岛素瘤之间的生长抑素受体 1-5 表达无差异。总之,GLP-1R 表达缺失与胰岛素瘤患者的转移疾病和生存不良相关。因此,GLP-1R 表达可能是评估肿瘤转移潜能和手术治疗患者预后的有用生物标志物。