Comprehensive analysis of DNA mismatch repair-deficient gastric cancer in a Japanese hospital-based population. (17th March 2021)

• Record Type: Journal Article
• Authors: Ito, Tetsuya; Suzuki, Okihide; Kamae, Nao; Tamaru, Jun-ichi; Arai, Tomio; Yamaguchi, Tatsuro; Akagi, Kiwamu; Eguchi, Hidetaka; Okazaki, Yasushi; Mochiki, Erito; Ishida, Hideyuki
• Is Part Of: Japanese journal of clinical oncology. Volume 51:Number 6(2021)
• Page Start: 886
• Page End: 894
• Publication Date: 2021-03-17
• Subjects: gastric cancer -- defective MMR -- anti-PD-1 blockade -- Lynch syndrome -- Lynch-like syndrome; Oncology -- Periodicals; Cancer -- Periodicals; 616.994005
• DOI: 10.1093/jjco/hyab026
• Languages: English
• ISSNs: 0368-2811

Abstract

Abstract: Background: The attention on mismatch repair-deficient (dMMR) gastric cancer has increased in this era of anti-PD-1 blockade therapy; however, the prevalence and molecular genetics of patients with dMMR gastric cancer have not been completely investigated. Methods: Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary gastric cancers of 513 consecutive patients. Genetic and/or epigenetic alterations of the MMR genes were also investigated. Results: Loss of expression of one or more MMR proteins was observed in 58 patients (11.3%); 54 patients showed loss of MLH1/PMS2, 3 patients showed loss of MLH1/PMS2/MSH6 and 1 patient showed loss of PMS2 alone. Among these 58 patients, 55 showed hypermethylation of the promoter region of MLH1 . Genetic testing revealed that the remaining three patients had Lynch syndrome ( n = 1) or Lynch-like syndrome ( n = 2). A total of 15 patients (25.9% of all patients with dMMR gastric cancer and 2.9% of all patients with gastric cancer), including 11 patients with stage I–III dMMR gastric cancer who had recurrence and 4 patients with stage IV dMMR gastric cancer, are potential candidates for the use of anti-PD-1 blockades. Conclusions: This is the first study to investigate the frequency and molecular genetic mechanisms of dMMR gastric cancer comprehensively, focusing on the benefit of using PD-1 blockades. Our observations will be beneficial in the clinical practice of metastatic gastric cancer. Abstract : The first study to investigate the frequency and molecular genetic mechanisms of mismatch repair-deficient gastric cancer comprehensively, focusing on the benefit of using PD-1 blockades.