Abstract
BackgroundGastric cancer develops even in Helicobacter pylori(H. 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 H. pylori-uninfected patients.MethodsSeventeen H. pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of H. pylori-infected patients with mucosal SRCCs. Seven SRCCs without H. pylori-infected, including two invasive SRCCs, and seven H. pylori-infected SRCCs were subjected to a genetic analysis using next-generation sequencing.ResultsH. pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the H. pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one H. pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without H. pylori-infected. 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.ConclusionsSome SRCCs in H. pylori-uninfected patients may have a malignant potential similar to that of SRCCs in H. pylori-infected patients. Smoking may not be the main carcinogenic factor for the development of SRCCs among the H. pylori-uninfected patients.
Highlights
Gastric cancer develops even in Helicobacter pylori(H. pylori)-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer
The features of SRCCs in H. pylori-uninfected patients resemble those in patients with hereditary diffuse gastric cancer (HDGC), which is caused by a germline mutation of CDH1 [7]
Clinical features in H. pylori-uninfected and -infected SRCCs First, we compared the clinicopathological features between 17 H. pylori-uninfected and -infected patients with SRCCs located within the mucosal layer
Summary
Gastric cancer develops even in Helicobacter pylori(H. pylori)-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. Gastric cancer may develop even in H. pylori-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer [4]. The features of SRCCs in H. pylori-uninfected patients resemble those in patients with hereditary diffuse gastric cancer (HDGC), which is caused by a germline mutation of CDH1 [7]. In patients with HDGC, a large number of SRCCs can be detected; most of them show little tendency to invade into the submucosal layer. It is controversial whether SRCCs in H. pylori-uninfected patients can invade into the submucosal layer. Horiuchi et al reported the implication of smoking in the disease pathogenesis of these patients, noting that their findings should be verified by other studies [8]
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