Immunohistochemical Glucagon-like Peptide-1 Receptor Expression in Human Insulinomas

Int J Mol Sci. 2023 Oct 13;24(20):15164. doi: 10.3390/ijms242015164.

Abstract

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.

Keywords: glucagon-like peptide-1 receptors; immunohistochemistry; insulinoma; neuroendocrine tumour.

MeSH terms

  • Antibodies, Monoclonal
  • Glucagon-Like Peptide-1 Receptor / genetics
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Insulin / metabolism
  • Insulinoma* / metabolism
  • Pancreatic Neoplasms* / metabolism
  • Retrospective Studies

Substances

  • Antibodies, Monoclonal
  • Glucagon-Like Peptide-1 Receptor
  • Insulin
  • GLP1R protein, human