[Real-World Data of Immunohistochemical Staining for DNA Mismatch Repair Proteins Highlight Candidates for Immune Checkpoint Inhibitor Treatment in Patients with Gastrointestinal Cancer].

Abstract

Overall assessment of KEYNOTE-164 study, KEYNOTE-158 study and CheckMate 142 study demonstrated the clinical benefits of immune checkpoint inhibitors(ICIs)among patients with mismatch repair deficient(dMMR)/high microsatellite instability(MSI-H)cancer. As a result, ICIs have been approved for treatment of MSI-H solid tumor regardless of the tumor type. However, the frequency of real-world diagnosed dMMR gastrointestinal cancer were rarely reported. Therefore, the results of immunohistochemical staining for DNA mismatch repair proteins was investigated. 175 samples of gastrointestinal cancers were examined between November 2019 and June 2023. Clinical and pathological characteristics were obtained from clinical and histopathological records. In real world populations with high proportion of elderly people, the frequency of diagnosed dMMR gastrointestinal cancer may be high compared with previous reports. Furthermore, based on the deficient pattern of mismatch repair protein and age, most cases classified as dMMR may be sporadic. Right side tumors and female may increase the likelihood of dMMR colorectal cancer. The current results justified immunohistochemical staining for DNA mismatch repair proteins, strongly involved in the appropriate patient selection for ICIs therapy, should be conducted for elderly patients newly diagnosed as gastrointestinal cancer. We believe that further clinical cancer immunology research, and then challenging insight targeting dMMR gastrointestinal cancer will result in future development of novel immunotherapy combination strategies well tolerated even in elderly patients.