Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 May 29;10(6):167.
doi: 10.3390/cancers10060167.

Clinical Importance of Epstein⁻Barr Virus-Associated Gastric Cancer

Jun Nishikawa  1 , Hisashi Iizasa  2 , Hironori Yoshiyama  3 , Kanami Shimokuri  4 , Yuki Kobayashi  5 , Sho Sasaki  6 , Munetaka Nakamura  7 , Hideo Yanai  8 , Kohei Sakai  9 , Yutaka Suehiro  10 , Takahiro Yamasaki  11 , Isao Sakaida  12
Affiliations
Review

Clinical Importance of Epstein⁻Barr Virus-Associated Gastric Cancer

Jun Nishikawa et al. Cancers (Basel). .

Abstract

Epstein⁻Barr virus-associated gastric carcinoma (EBVaGC) is the most common malignancy caused by EBV infection. EBVaGC has definite histological characteristics similar to gastric carcinoma with lymphoid stroma. Clinically, EBVaGC has a significantly low frequency of lymph node metastasis compared with EBV-negative gastric cancer, resulting in a better prognosis. The Cancer Genome Atlas of gastric adenocarcinomas proposed a molecular classification divided into four molecular subtypes: (1) EBVaGC; (2) microsatellite instability; (3) chromosomal instability; and (4) genomically stable tumors. EBVaGC harbors a DNA methylation phenotype, PD-L1 and PD-L2 overexpression, and frequent alterations in the PIK3CA gene. We review clinical importance of EBVaGC and discuss novel therapeutic applications for EBVaGC.

Keywords: DNA methylation; Epstein–Barr virus; endoscopic mucosal resection (EMR); endoscopic submucosal dissection (ESD); gastric carcinoma; immune checkpoint inhibitor; programed cell death 1 (PD-1); programmed cell death ligand 1 (PD-L1).

PubMed Disclaimer

Conflict of interest statement

The authors declare no financial or commercial conflicts of interest.

Figures

Figure 1
Figure 1
Histologic characteristic of Epstein–Barr virus-associated gastric carcinoma (EBVaGC). (a) EBV-encoded small ribonucleic acid (EBER1) in situ hybridization shows positive nuclei in the carcinoma cells, which are surrounded by infiltrating lymphocytes (×100); (b) Histologic characteristic of EBVaGC. The “lacy pattern” is composed of irregularly anastomosing tubules and moderate to dense lymphocytic infiltration (×100).
Figure 2
Figure 2
Endoscopic images of an EBV-associated gastric carcinoma. Submucosal tumor-like morphology is one of the features of EBVaGC.
Figure 3
Figure 3
Treatment by DNA demethylating agents for EBVaGC.
Figure 4
Figure 4
Treatment by blocking PD-1/PD-L1 for EBVaGC.
See this image and copyright information in PMC

References

    1. Zur Hausen H., Schulte-Holthausen H., Klein G., Henle W., Henle G., Clifford P., Santesson L. EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature. 1970;228:1056–1058. doi: 10.1038/2281056a0. - DOI - PubMed
    1. Rickinson A.B., Kieff E. Epstein-Barr virus. In: Fields B.N., Knipe D.M., Howley P.M., editors. Fields Virology. 5th ed. Volume 2. Lippincott-Williams & Wilkins; Philadelphia, PA, USA: 2007. pp. 2655–2700.
    1. Van Cutsem E., Sagaert X., Topal B., Haustermans K., Prenen H. Gastric cancer. Lancet. 2016;388:2654–2664. doi: 10.1016/S0140-6736(16)30354-3. - DOI - PubMed
    1. Murphy G., Pfeiffer R., Camargo M.C., Rabkin C.S. Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology. 2009;137:824–833. doi: 10.1053/j.gastro.2009.05.001. - DOI - PMC - PubMed
    1. Cancer Genome Atlas Research Network Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–209. - PMC - PubMed