Endocrine Abstracts

Insulinomas are rare insulin-producing pancreatic neuroendocrine tumours. Most insulinomas are non-metastatic and can be cured by surgery, but in 10% of the patients insulinomas metastasize, which is associated with a significantly impaired overall survival. As the metastatic potential of an insulinoma cannot be reliably predicted with the current biomarkers, we aimed to evaluate the expression of somatostatin receptors (SSTRs) and glucagon-like peptide-1 receptors (GLP-1Rs) in insulinomas and to analyse their association with clinicopathological features and long-term patient outcome^1,2. The study material included formalin-fixed paraffin-embedded primary tumour tissue samples of 52 insulinoma patients diagnosed in Finland 1980–2010. Of these patients, 47 had a sporadic, non-metastatic insulinoma, 3 had a sporadic, metastatic insulinoma and 2 patients had a MEN1-syndrome-related, non-metastatic insulinoma. The median duration of the register-based follow-up was 10 (0–32) years after surgery. After histological re-evaluation, the samples were processed into tissue microarrays (TMA) and stained immunohistochemically with monoclonal SSTR1-5 and GLP-1R antibodies. The scoring was made manually and the immunoreactivity of the strongest stained TMA spot was scored based on membranous staining for GLP-1Rs and on both membranous and cytoplasmic staining for SSTRs. Of the somatostatin receptors, SSTR2 was expressed most frequently (71%), followed by SSTR3 (33%), SSTR1 (27%) and SSTR5 (6%). SSTR3 expression was associated with a larger tumour size, and SSTR3 and SSTR5 expression were associated with impaired overall survival. The expression of GLP-1Rs differed significantly between metastatic and non-metastatic insulinomas, as all sporadic, non-metastatic insulinomas expressed GLP-1R, while all metastatic insulinomas lacked the expression of GLP-1R. Of the two non-metastatic, MEN1-related insulinomas, one expressed GLP-1R and the other did not. In conclusion, the lack of GLP-1R expression is associated with a metastatic disease and impaired survival. Our results indicate that the lack of GLP-1R expression could be used as a negative prognostic marker in insulinomas but additional studies investigating a higher number of metastatic insulinomas are needed. Regarding SSTRs, most insulinomas were found to express SSTR subtype 2, which may be utilized in SSTR-targeted imaging and treatment, but further studies are needed to clarify the association between SSTR expression profile and overall survival.

References: 1. Vesterinen T, Peltola E, et al. Immunohistochemical Glucagon-like Peptide-1 Receptor Expression in Human Insulinomas. International Journal of Molecular Sciences. 2023; 24(20):15164. DOI: 10.3390/ijms242015164.

2. Peltola E, Vesterinen T, et al. Immunohistochemical somatostatin receptor expression in insulinomas. APMIS 2023; 131(4): 152-160. DOI: 10.1111/apm. 13297.