PD-L1, MMR, and EGFR expression in gastrointestinal neuroendocrine tumors

Abstract

Purpose: There are limited studies on gastrointestinal neuroendocrine tumors (NETs) in the literature. This study aimed to determine PD-L1 and EGFR expression in primary G1 and G2 NETs and neuroendocrine carcinoma located in the gastrointestinal system, explore the relationship between grades, and investigate the loss of DNA mismatch repair (MMR) protein expression and its association with PD-L1 expression. Materials and Methods: All patients diagnosed with primary gastrointestinal NETs between January 2017 and January 2021 were included in this study. The study evaluated the protein expression of PD-L1, EGFR, MLH1, MSH2, MSH6, and PMS2 by immunohistochemistry. A total of 30 patients were included in the study. Results: PD-L1 expression was detected in tumor cells and/or tumor microenvironment immune cells in 8 cases (28%), consisting of four G1, two G2, and two NEC cases. There was no significant relationship between histological grade and PD-L1 expression. A loss of expression of at least one MMR protein was noted in 16 cases (53%). A loss of MMR protein expression was detected in five of the eight cases with PD-L1 expression. EGFR expression was not detected in any of the cases. Conclusion: The study revealed a loss of MMR protein expression in 53% and PD-L1 expression in 27% of gastrointestinal NETs. This study might be a pioneer for future studies on immune checkpoint inhibitors in microsatellite-unstable NETs, thereby contributing to providing a treatment alternative for this group of patients.