Clinicopathological and Molecular Characterization of Early Gastric Adenocarcinoma in Helicobacter Pylori-uninfected Patients: Emphasis on Differentiated Gastric Adenocarcinoma

Overview

Journal J Gastroenterol

Specialty Gastroenterology

Date 2022 Aug 8

PMID 35939123

Authors

Yoichi Akazawa

Hiroya Ueyama

Takuo Hayashi

Hisanori Utsunomiya

Ryota Uchida

Daiki Abe

Shotaro Oki

Nobuyuki Suzuki

Atsushi Ikeda

Noboru Yatagai

Hiroyuki Komori

Tsutomu Takeda

Kohei Matsumoto

Kumiko Ueda

Kenshi Matsumoto

Daisuke Asaoka

Mariko Hojo

Tsuyoshi Saito

Takashi Yao

Akihito Nagahara

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Intestinal metaplasia key molecules and UPP1 activation via Helicobacter pylori /NF-kB: drivers of malignant progression in gastric cancer.

Chen X, Zhou B, Wang S, Jiang X, Ping Y, Xia J Cancer Cell Int. 2024; 24(1):399.

PMID: 39695769 PMC: 11657005. DOI: 10.1186/s12935-024-03598-6.

Trends of Early -Uninfected Gastric Cancer in an Aging Regional Area.

Maeda H, Sasaki F, Ooi T, Uehara S, Yano H, Sameshima Y J Clin Med. 2024; 13(6).

PMID: 38542051 PMC: 10971114. DOI: 10.3390/jcm13061827.

Clinicopathological and endoscopic features of Helicobacter pylori infection-negative gastric cancer in Japan: a retrospective study.

Imamura K, Yao K, Nimura S, Kanemitsu T, Miyaoka M, Ono Y Clin Endosc. 2024; 57(4):486-494.

PMID: 38514987 PMC: 11294854. DOI: 10.5946/ce.2023.258.

Prevalence of Gastric Epithelial Tumors in Helicobacter pylori-uninfected Individuals Undergoing a Medical Checkup.

Okimoto E, Adachi K, Ebisutani Y, Ishimura N, Ishihara S Intern Med. 2024; 63(16):2251-2258.

PMID: 38220193 PMC: 11414374. DOI: 10.2169/internalmedicine.2955-23.

Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and -naïve patients: a multicenter retrospective analysis.

Kotani S, Shibagaki K, Hirahara N, Hasegawa N, Tanabe R, Ebisutani Y J Gastroenterol. 2023; 59(1):1-10.

PMID: 37855982 DOI: 10.1007/s00535-023-02050-2.

References

Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M . Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001; 345(11):784-9. DOI: 10.1056/NEJMoa001999. View

Matsuo T, Ito M, Takata S, Tanaka S, Yoshihara M, Chayama K . Low prevalence of Helicobacter pylori-negative gastric cancer among Japanese. Helicobacter. 2011; 16(6):415-9. DOI: 10.1111/j.1523-5378.2011.00889.x. View

Yamamoto Y, Fujisaki J, Omae M, Hirasawa T, Igarashi M . Helicobacter pylori-negative gastric cancer: characteristics and endoscopic findings. Dig Endosc. 2015; 27(5):551-61. DOI: 10.1111/den.12471. View

Yamada A, Kaise M, Inoshita N, Toba T, Nomura K, Kuribayashi Y . Characterization of Helicobacter pylori-Naïve Early Gastric Cancers. Digestion. 2018; 98(2):127-134. DOI: 10.1159/000487795. View

Horiuchi Y, Fujisaki J, Ishizuka N, Omae M, Ishiyama A, Yoshio T . Study on Clinical Factors Involved in Helicobacter pylori-Uninfected, Undifferentiated-Type Early Gastric Cancer. Digestion. 2017; 96(4):213-219. DOI: 10.1159/000481817. View

Ueyama H, Yao T, Nakashima Y, Hirakawa K, Oshiro Y, Hirahashi M . Gastric adenocarcinoma of fundic gland type (chief cell predominant type): proposal for a new entity of gastric adenocarcinoma. Am J Surg Pathol. 2010; 34(5):609-19. DOI: 10.1097/PAS.0b013e3181d94d53. View

Yorita N, Ito M, Boda T, Kotachi T, Nagasaki N, Abuduwaili M . Potential of Helicobacter pylori-uninfected signet ring cell carcinoma to invade the submucosal layer. J Gastroenterol Hepatol. 2019; 34(11):1955-1962. DOI: 10.1111/jgh.14706. View

Ueyama H, Yao T, Akazawa Y, Hayashi T, Kurahara K, Oshiro Y . Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type. J Gastroenterol. 2021; 56(9):814-828. PMC: 8370942. DOI: 10.1007/s00535-021-01813-z. View

Ueyama H, Matsumoto K, Nagahara A, Hayashi T, Yao T, Watanabe S . Gastric adenocarcinoma of the fundic gland type (chief cell predominant type). Endoscopy. 2013; 46(2):153-7. DOI: 10.1055/s-0033-1359042. View

10.

Ozaki Y, Suto H, Nosaka T, Saito Y, Naito T, Takahashi K . A case of Helicobacter pylori-negative intramucosal well-differentiated gastric adenocarcinoma with intestinal phenotype. Clin J Gastroenterol. 2015; 8(1):18-21. DOI: 10.1007/s12328-014-0543-x. View

11.

Kotani S, Miyaoka Y, Fujiwara A, Tsukano K, Ogawa S, Yamanouchi S . Intestinal-type gastric adenocarcinoma without Helicobacter pylori infection successfully treated with endoscopic submucosal dissection. Clin J Gastroenterol. 2016; 9(4):228-32. DOI: 10.1007/s12328-016-0654-7. View

12.

Yoshii S, Hayashi Y, Takehara T . Helicobacter pylori-negative early gastric adenocarcinoma with complete intestinal mucus phenotype mimicking verrucous gastritis. Dig Endosc. 2016; 29(2):235-236. DOI: 10.1111/den.12782. View

13.

Shibagaki K, Fukuyama C, Mikami H, Izumi D, Yamashita N, Mishiro T . Gastric foveolar-type adenomas endoscopically showing a raspberry-like appearance in the -uninfected stomach. Endosc Int Open. 2019; 7(6):E784-E791. PMC: 6561766. DOI: 10.1055/a-0854-3818. View

14.

Isono Y, Baba Y, Mukai K, Asakawa H, Nose K, Tsuruga S . Gastric adenocarcinoma coexisting with a reddish semipedunculated polyp arising from Helicobacter pylori-negative normal gastric mucosa: a report of two cases. Clin J Gastroenterol. 2018; 11(6):481-486. DOI: 10.1007/s12328-018-0887-8. View

15.

Takita M, Ohata K, Inamoto R, Kurebayashi M, Takayanagi S, Kimoto Y . Endoscopic and histological features of negative differentiated gastric adenocarcinoma arising in the antrum. JGH Open. 2021; 5(4):470-477. PMC: 8035464. DOI: 10.1002/jgh3.12518. View

16.

Yoshida T, Yamaguchi T, Maekawa S, Takano S, Kuno T, Tanaka K . Identification of early genetic changes in well-differentiated intramucosal gastric carcinoma by target deep sequencing. Gastric Cancer. 2019; 22(4):742-750. DOI: 10.1007/s10120-019-00926-y. View

17.

Benedict M, Lauwers G, Jain D . Gastric Adenocarcinoma of the Fundic Gland Type: Update and Literature Review. Am J Clin Pathol. 2018; 149(6):461-473. DOI: 10.1093/ajcp/aqy019. View

18.

Akazawa Y, Saito T, Hayashi T, Yanai Y, Tsuyama S, Akaike K . Next-generation sequencing analysis for gastric adenocarcinoma with enteroblastic differentiation: emphasis on the relationship with hepatoid adenocarcinoma. Hum Pathol. 2018; 78:79-88. DOI: 10.1016/j.humpath.2018.04.022. View

19.

Kishikawa S, Hayashi T, Saito T, Takamochi K, Kohsaka S, Sano K . Diffuse expression of MUC6 defines a distinct clinicopathological subset of pulmonary invasive mucinous adenocarcinoma. Mod Pathol. 2020; 34(4):786-797. DOI: 10.1038/s41379-020-00690-w. View

20.

Bonneville R, Krook M, Kautto E, Miya J, Wing M, Chen H . Landscape of Microsatellite Instability Across 39 Cancer Types. JCO Precis Oncol. 2018; 2017. PMC: 5972025. DOI: 10.1200/PO.17.00073. View