Clinicopathological and molecular characterization of early gastric adenocarcinoma in Helicobacter pylori-uninfected patients: emphasis on differentiated gastric adenocarcinoma

• Published in: Journal of gastroenterology 2022-10, Vol.57 (10), p.725-734
• Main Authors: Akazawa, Yoichi, Ueyama, Hiroya, Hayashi, Takuo, Utsunomiya, Hisanori, Uchida, Ryota, Abe, Daiki, Oki, Shotaro, Suzuki, Nobuyuki, Ikeda, Atsushi, Yatagai, Noboru, Komori, Hiroyuki, Takeda, Tsutomu, Matsumoto, Kohei, Ueda, Kumiko, Matsumoto, Kenshi, Asaoka, Daisuke, Hojo, Mariko, Saito, Tsuyoshi, Yao, Takashi, Nagahara, Akihito
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Adenocarcinoma; Adenomatous polyposis coli; Cancer; Carcinoma; Colorectal Surgery; Core protein; Endoscopy; Gastric cancer; Gastric mucosa; Gastroenterology; Genotype & phenotype; Helicobacter pylori; Hepatology; Medicine; Medicine & Public Health; Mucins; Next-generation sequencing; Original Article—Alimentary Tract; Phenotypes; Stomach cancer; Surgical Oncology
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-022-01906-3

Background Recently, Helicobacter pylori (HP) -uninfected gastric mucosal cancer has been reported; however, the clinicopathological and molecular features of HP -uninfected gastric cancer have not been elucidated. Methods We evaluated the clinicopathological, immunohistochemical, and genetic alterations in HP -uninfected early gastric adenocarcinoma using next-generation sequencing (NGS). Results Among 968 primary early gastric carcinomas, 64 (6.6%) were HP -uninfected gastric adenocarcinoma and were pathologically classified as gastric adenocarcinoma of fundic-gland type (GA-FG, n  = 39), differentiated gastric adenocarcinoma (DGA, n  = 16), and signet-ring cell carcinoma (SRCC, n  = 9). Based on the expression profile of the mucin core protein, DGAs were classified into a gastrointestinal phenotype showing either MUC5AC or MUC6 expression and MUC2 or CD10 expression simultaneously ( n  = 5), and a gastric phenotype ( n  = 11) showing either MUC5AC or MUC6 expression. All DGAs with a gastrointestinal phenotype shared similar endoscopic characteristics, such as reddish depressed lesions in the antrum. In contrast, DGAs with a gastric phenotype exhibited several distinct endoscopic features, including a raspberry-shaped appearance and whitish flat-elevated appearance; the former expressed only MUC5AC and the latter exhibited co-expression of MUC5AC and MUC6. Among 16 HP -uninfected DGAs, seven were subjected to NGS. APC was recurrently mutated in DGA (42.9%) and was enriched in DGAs with a gastrointestinal phenotype (75%). Conclusions Overall, HP -uninfected gastric adenocarcinomas showed distinct clinicopathologic and endoscopic characteristics. Furthermore, HP -uninfected DGAs, especially those with a gastrointestinal phenotype, may be characterized by recurrent APC mutations.