Prevalence of microsatellite instability, Lynch syndrome, and PD-L1 expression in patients with Epstein–Barr virus negative gastric carcinoma with lymphoid stroma

Abstract Purpose The prevalence of the Lynch syndrome and microsatellite instability (MSI) among patients with gastric carcinoma with lymphoid stroma (GCLS) is poorly understood. The present study aimed to investigate MSI and programmed death-ligand 1 (PD-L1) expression and further evaluate Lynch syndrome in patients with GCLS. Methods The study included 104 patients with GCLS (30 EBV-negative and 74 EBV-positive cases) who underwent surgical resection. Immunohistochemistry for mismatch repair proteins and PD-L1 (SP263), along with MSI testing, were performed. Whole-exome sequencing was performed for patients suspected of having Lynch syndrome. Results Compared with patients with EBV-positive GCLS, patients with EBV-negative GCLS were more likely to be older, female, and have a higher rate of MSI-high (MSI-H) phenotype incidence, with a primary tumour site predisposition to the distal stomach. They also tended to have a history of metachronous cancers and high expression of the PD-L1 protein. Fifteen (50%) of the 30 cases were of the MSI-H phenotype with loss of MLH1 and PMS2 expression. Among them, two (6.7%) patients were found to have Lynch syndrome with germline mutations in MLH1 and PMS2. Conclusions Evaluation of MSI is highly recommended in patients with EBV-negative GCLS. In patients with MSI-H tumours, selective genetic consultation and testing are required to detect Lynch syndrome. In addition, the rate of PD-L1 positivity in both EBV-negative and EBV-positive GCLS was relatively high (13.3% and 29.7%, respectively). Therefore, patients with GCLS, regardless of EBV infection, can be good candidates for treatment with immune checkpoint inhibitors.