Clinical and molecular characteristics of mucosal signet-ring cell carcinoma in Helicobacter pylori-uninfected stomach

Abstract Background: Gastric cancer develops even in Helicobacter pylori -uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in Helicobacter pylori -uninfected patients. Methods: Seventeen Helicobacter pylori -uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of Helicobacter pylori -infected patients with mucosal SRCCs. Seven SRCCs without Helicobacter pylori infection, including two invasive SRCCs, and seven Helicobacter pylori -positive SRCCs were subjected to a genetic analysis using next-generation sequencing. Results: Helicobacter pylori -uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the Helicobacter pylori -infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one Helicobacter pylori -uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without Helicobacter pylori infection. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smoking-induced mutation, was not found in any of the samples. Conclusions: Some SRCCs in Helicobacter pylori -uninfected patients may have a malignant potential similar to that of SRCCs in Helicobacter pylori -infected patients. Smoking is not a main carcinogenic factor for the development of SRCCs.