Immunohistochemical and in situ hybridization analyses of glucose transporter 2 in pancreatic neuroendocrine tumors: Possible glucose transporter 2 association with neoplastic insulin production

Background: Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms. Additionally, glucose transporter 2 (GLUT2) is associated with insulin production and is essential for glucose transport to normal pancreatic beta-cells. Neoplastic cell GLUT2 expression may also influence insulin production by using this transporter. GLUT2 expression and its clinical significance remain unclear in PanNETs. This study aimed to provide GLUT2 expression profiles and evidence of correlation with insulin in PanNETs.Methods: Clinical data were retrieved from 113 surgically resected paraffin-embedded PanNET tissue samples fixed with 10% formalin. PanNETs are categorized as insulinoma, non-functional (NF)-PanNET, or PanNET-not otherwise specified (NOS). A GLUT2 score was used to evaluate cytoplasmic GLUT2 immunoreactivity. The immunoreactive score (IRS) was used to determine membranous GLUT2, cytoplasmic insulin, and proinsulin immunoreactivities. A commercially available in situ hybridization (ISH) kit detected human SLC2A2 (GLUT2) mRNA on tissues in all seven positive-and 20 negative-GLUT2 IRS cases. Results: GLUT2 and IRSs significantly differed among insulinoma, NF-PanNET, and PanNET-NOS. Insulinomas exhibited significantly higher GLUT2 scores and IRSs than did NF-PanNETs. GLUT2 IRS positive cases demon-strated significantly higher insulin and proinsulin IRSs than did negative cases. Additionally, GLUT2 ISH-positive cases demonstrated positive GLUT2 scores and IRSs, with significantly higher GLUT2 IRSs than did negative cases. PanNET histological grade categories did not significantly affect GLUT2 scores and IRSs. Conclusion: The first evidence of a correlation between GLUT2 expressions and insulin in PanNETs is shown in this study.