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Epstein–Barr virus status is a promising biomarker for endoscopic resection in early gastric cancer: proposal of a novel therapeutic strategy

  • Hiroki Osumi
  • Hiroshi Kawachi
  • Toshiyuki YoshioEmail author
  • Satoshi Ida
  • Noriko Yamamoto
  • Yusuke Horiuchi
  • Akiyoshi Ishiyama
  • Toshiaki Hirasawa
  • Tomohiro Tsuchida
  • Naoki Hiki
  • Kengo Takeuchi
  • Junko Fujisaki
Original Article—Alimentary Tract
  • 153 Downloads

Abstract

Background

Epstein–Barr virus-positive gastric cancer (EBVGC) is associated with a low prevalence of lymph node metastasis (LNM); however, EBV status is not considered in the indication of endoscopic resection (ER). We aimed to clarify the implication of EBV status for ER of pT1b GC.

Methods

Consecutive cases of pT1b GCs treated with surgery between 2005 and 2014 were retrospectively analyzed. Clinicopathological factors and LNM status were compared between EBVGC and non-EBVGC groups.

Results

EBVGC accounted for 7.9% (71 of 898) cases. Compared to non-EBVGC, EBVGC was more frequent in males (p = 0.0055), the upper third region (p < 0.0001), showed elevated growth features (p = 0.0059), and was associated with a lower frequency of accompanying ulceration (p = 0.002), greater depth of submucosal invasion (p = 0.017), and lower frequency of lymphatic invasion (p < 0.0001). Frequency of LNM was significantly lower in EBVGC than in non-EBVGC (4.2% vs. 21.9%, p < 0.0001). In EBVGC, tumors without lymphovascular invasion showed significantly lower frequency of LNM than those with lymphovascular invasion (0 of 50, 0%; vs 3 of 21, 14.3%; p = 0.023). Histologically, 84.5% (60 of 71) of EBVGC included carcinomas with lymphoid stroma and/or lace pattern components.

Conclusions

pT1b EBVGC is a convincing candidate for ER, regardless of risk factors other than lymphovascular invasion.

Keywords

Gastric carcinoma pT1b Epstein–Barr virus Lymph node metastasis 

Notes

Acknowledgements

We are grateful to Ms. Miyuki Kogure, Mr. Motoyoshi Iwakoshi, Ms. Tomoyo Kakita, Ms. Miki Hatta, Mr. Shuhei Ishii, and Ms. Naoko Takahashi for their excellent technical support. We also thank Dr. Maki Kobayashi for strong support and advice regarding the histologic analysis.

Author contributions

Conception and design: HO, HK, TY and JF; acquisition of data: HO; analysis and interpretation of data: HO, HK, TY; writing, review and/or revision of the manuscript: all authors; administrative, technical or material support: HK and NY; study supervision: JF.

Funding

This research was supported by the Daiwa Securities Health Foundation and JSPS KAKENHI Grant number JP16K08661.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Institutional Review Board, approval number 2017-1078) and with the Helsinki Declaration.

Supplementary material

535_2019_1562_MOESM1_ESM.tiff (10 mb)
Figure S1: Typical endoscopic image of EBVGC. Superficial depressed type (0-IIc) are the most common macroscopic EBVGC (A). EBVGC with invasion to the deep submucosa results in submucosal tumor-like protrusions due to the prominent proliferation of lymphoid tissue around poorly cohesive cancer tissue (carcinoma with lymphoid stroma) (B). Abbreviations: EBV, Epstein–Barr virus; EBER-ISH, EBV-Encoded RNA in situ hybridization; EBVGC, EBV gastric cancer (TIFF 6594 kb)
535_2019_1562_MOESM2_ESM.xlsx (10 kb)
Supplementary material 2 (XLSX 10 kb)
535_2019_1562_MOESM3_ESM.xlsx (10 kb)
Supplementary material 3 (XLSX 10 kb)

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Copyright information

© Japanese Society of Gastroenterology 2019

Authors and Affiliations

  • Hiroki Osumi
    • 1
  • Hiroshi Kawachi
    • 2
  • Toshiyuki Yoshio
    • 1
    Email author
  • Satoshi Ida
    • 3
  • Noriko Yamamoto
    • 2
  • Yusuke Horiuchi
    • 1
  • Akiyoshi Ishiyama
    • 1
  • Toshiaki Hirasawa
    • 1
  • Tomohiro Tsuchida
    • 1
  • Naoki Hiki
    • 3
  • Kengo Takeuchi
    • 2
  • Junko Fujisaki
    • 1
  1. 1.Department of GastroenterologyThe Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR)TokyoJapan
  2. 2.Department of PathologyThe Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR)TokyoJapan
  3. 3.Department of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR)TokyoJapan

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