PMID- 37894845 OWN - NLM STAT- MEDLINE DCOM- 20231030 LR - 20231030 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 20 DP - 2023 Oct 13 TI - Immunohistochemical Glucagon-like Peptide-1 Receptor Expression in Human Insulinomas. LID - 10.3390/ijms242015164 [doi] LID - 15164 AB - 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. FAU - Vesterinen, Tiina AU - Vesterinen T AUID- ORCID: 0000-0003-2997-0337 AD - Department of Pathology, HUSLAB, HUS Diagnostic Center, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland. AD - Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00290 Helsinki, Finland. FAU - Peltola, Elina AU - Peltola E AUID- ORCID: 0000-0003-3359-7109 AD - Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland. AD - Department of Internal Medicine, Tampere University Hospital, 33520 Tampere, Finland. FAU - Leijon, Helena AU - Leijon H AD - Department of Pathology, HUSLAB, HUS Diagnostic Center, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland. FAU - Hannula, Paivi AU - Hannula P AUID- ORCID: 0000-0003-3172-9331 AD - Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland. AD - Endocrinology, Department of Internal Medicine, Tampere University Hospital, 33520 Tampere, Finland. FAU - Huhtala, Heini AU - Huhtala H AUID- ORCID: 0000-0003-1372-430X AD - Faculty of Social Sciences, Tampere University, 33014 Tampere, Finland. FAU - Makinen, Markus J AU - Makinen MJ AD - Department of Pathology, Research Unit of Translational Medicine, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland. FAU - Nieminen, Lasse AU - Nieminen L AD - Fimlab Laboratories, Pathology Department, Tampere University Hospital, 33520 Tampere, Finland. FAU - Pirinen, Elina AU - Pirinen E AD - Department of Clinical Pathology, Kuopio University Hospital, 70029 Kuopio, Finland. FAU - Ronty, Mikko AU - Ronty M AD - Department of Pathology, HUSLAB, HUS Diagnostic Center, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland. FAU - Soderstrom, Mirva AU - Soderstrom M AD - Department of Pathology, Turku University Hospital, 20521 Turku, Finland. FAU - Jaatinen, Pia AU - Jaatinen P AUID- ORCID: 0000-0002-8693-3498 AD - Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland. AD - Department of Internal Medicine, Tampere University Hospital, 33520 Tampere, Finland. AD - Division of Internal Medicine, Seinajoki Central Hospital, 60220 Seinajoki, Finland. FAU - Arola, Johanna AU - Arola J AD - Department of Pathology, HUSLAB, HUS Diagnostic Center, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland. LA - eng GR - no number/the Finnish Cancer Foundation/ GR - TYH2021204/the Helsinki University Hospital Research Fund/ GR - 1717/6143/the Hospital District of South Ostrobothnia/ GR - UCS2023 Funding/Research Funding provided by Tampere University and the University Consortium of Seinajoki/ GR - 6300/3247 and MK287/Research Funding provided by Tampere University Hospital/ PT - Journal Article DEP - 20231013 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antibodies, Monoclonal) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Insulin) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - Antibodies, Monoclonal MH - Glucagon-Like Peptide-1 Receptor/genetics/metabolism MH - Insulin/metabolism MH - *Insulinoma/metabolism MH - *Pancreatic Neoplasms/metabolism MH - Retrospective Studies PMC - PMC10606800 OTO - NOTNLM OT - glucagon-like peptide-1 receptors OT - immunohistochemistry OT - insulinoma OT - neuroendocrine tumour COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2023/10/28 11:43 MHDA- 2023/10/30 06:46 PMCR- 2023/10/13 CRDT- 2023/10/28 01:18 PHST- 2023/08/23 00:00 [received] PHST- 2023/10/04 00:00 [revised] PHST- 2023/10/11 00:00 [accepted] PHST- 2023/10/30 06:46 [medline] PHST- 2023/10/28 11:43 [pubmed] PHST- 2023/10/28 01:18 [entrez] PHST- 2023/10/13 00:00 [pmc-release] AID - ijms242015164 [pii] AID - ijms-24-15164 [pii] AID - 10.3390/ijms242015164 [doi] PST - epublish SO - Int J Mol Sci. 2023 Oct 13;24(20):15164. doi: 10.3390/ijms242015164.