Epstein–Barr virus positivity, not mismatch repair-deficiency, is a favorable risk factor for lymph node metastasis in submucosa-invasive early gastric cancer

Ji Hye Park, Eunkyung Kim, Yon Hee Kim, Jie-Hyun Kim, Yoon Sung Bae, Yongchan Lee, Jae Ho Cheong, Sung Hoon Noh, Hyunki Kim

Research output: Contribution to journalArticle

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Abstract

Background: Epstein–Barr virus (EBV)-associated gastric cancer (GC) and microsatellite-instability-high GC are associated with a low prevalence of regional lymph node metastasis (LNM). To evaluate the feasibility of endoscopic treatment of EBV-associated and/or microsatellite-instability-high early GC (EGC), we analyzed the risk factors for LNM using a large series (n = 756) of submucosa-invasive (SM) EGC. Methods: EBV-encoded RNA in situ hybridization (EBER ISH) and immunohistochemistry for four mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6) were performed. The clinicopathologic features and results of EBER ISH and immunohistochemistry were compared according to the LNM status. Results: Among the cases, 146 EGCs (19.3 %) showed LNM. EBV negativity, larger tumor size (greater than 2 cm), deeper level of submucosal invasion, submucosal invasion depth greater than 500 µm, presence of ulceration, and presence of lymphovascular invasion (LVI) were associated with LNM. However, the MMR deficiency was not correlated with LNM. On multivariate regression analysis, larger tumor size (greater than 2 cm; odds ratio 1.6, p = 0.030), deeper level of submucosal invasion (odds ratio 2.9, p = 0.001), LVI (odds ratio 7.4, p < 0.001), and EBV negativity (p = 0.020) were independent risk factors for LNM in SM EGCs. Conclusions: EBV positivity was a favorable risk factor for LNM in SM EGC. However, MMR deficiency was not associated with the status of LNM. Thus, we suggest that examination with EBER ISH could be considered for endoscopic resected specimens, especially in cases of SM EGC showing no LVI and clear resection margins.

Original languageEnglish
Pages (from-to)1041-1051
Number of pages11
JournalGastric Cancer
Volume19
Issue number4
DOIs
Publication statusPublished - 2016 Oct 1

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Stomach Neoplasms
Lymph Nodes
Neoplasm Metastasis
Viruses
In Situ Hybridization
Microsatellite Instability
Human Herpesvirus 4
Immunohistochemistry
RNA
Turcot syndrome
DNA Mismatch Repair
RNA Viruses
Neoplasms
Multivariate Analysis
Odds Ratio
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

@article{47ad4a4f26e4435a9ac59f91886d87c1,
title = "Epstein–Barr virus positivity, not mismatch repair-deficiency, is a favorable risk factor for lymph node metastasis in submucosa-invasive early gastric cancer",
abstract = "Background: Epstein–Barr virus (EBV)-associated gastric cancer (GC) and microsatellite-instability-high GC are associated with a low prevalence of regional lymph node metastasis (LNM). To evaluate the feasibility of endoscopic treatment of EBV-associated and/or microsatellite-instability-high early GC (EGC), we analyzed the risk factors for LNM using a large series (n = 756) of submucosa-invasive (SM) EGC. Methods: EBV-encoded RNA in situ hybridization (EBER ISH) and immunohistochemistry for four mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6) were performed. The clinicopathologic features and results of EBER ISH and immunohistochemistry were compared according to the LNM status. Results: Among the cases, 146 EGCs (19.3 {\%}) showed LNM. EBV negativity, larger tumor size (greater than 2 cm), deeper level of submucosal invasion, submucosal invasion depth greater than 500 µm, presence of ulceration, and presence of lymphovascular invasion (LVI) were associated with LNM. However, the MMR deficiency was not correlated with LNM. On multivariate regression analysis, larger tumor size (greater than 2 cm; odds ratio 1.6, p = 0.030), deeper level of submucosal invasion (odds ratio 2.9, p = 0.001), LVI (odds ratio 7.4, p < 0.001), and EBV negativity (p = 0.020) were independent risk factors for LNM in SM EGCs. Conclusions: EBV positivity was a favorable risk factor for LNM in SM EGC. However, MMR deficiency was not associated with the status of LNM. Thus, we suggest that examination with EBER ISH could be considered for endoscopic resected specimens, especially in cases of SM EGC showing no LVI and clear resection margins.",
author = "Park, {Ji Hye} and Eunkyung Kim and Kim, {Yon Hee} and Jie-Hyun Kim and Bae, {Yoon Sung} and Yongchan Lee and Cheong, {Jae Ho} and Noh, {Sung Hoon} and Hyunki Kim",
year = "2016",
month = "10",
day = "1",
doi = "10.1007/s10120-015-0565-1",
language = "English",
volume = "19",
pages = "1041--1051",
journal = "Gastric Cancer",
issn = "1436-3291",
publisher = "Springer Japan",
number = "4",

}

Epstein–Barr virus positivity, not mismatch repair-deficiency, is a favorable risk factor for lymph node metastasis in submucosa-invasive early gastric cancer. / Park, Ji Hye; Kim, Eunkyung; Kim, Yon Hee; Kim, Jie-Hyun; Bae, Yoon Sung; Lee, Yongchan; Cheong, Jae Ho; Noh, Sung Hoon; Kim, Hyunki.

In: Gastric Cancer, Vol. 19, No. 4, 01.10.2016, p. 1041-1051.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Epstein–Barr virus positivity, not mismatch repair-deficiency, is a favorable risk factor for lymph node metastasis in submucosa-invasive early gastric cancer

AU - Park, Ji Hye

AU - Kim, Eunkyung

AU - Kim, Yon Hee

AU - Kim, Jie-Hyun

AU - Bae, Yoon Sung

AU - Lee, Yongchan

AU - Cheong, Jae Ho

AU - Noh, Sung Hoon

AU - Kim, Hyunki

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Background: Epstein–Barr virus (EBV)-associated gastric cancer (GC) and microsatellite-instability-high GC are associated with a low prevalence of regional lymph node metastasis (LNM). To evaluate the feasibility of endoscopic treatment of EBV-associated and/or microsatellite-instability-high early GC (EGC), we analyzed the risk factors for LNM using a large series (n = 756) of submucosa-invasive (SM) EGC. Methods: EBV-encoded RNA in situ hybridization (EBER ISH) and immunohistochemistry for four mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6) were performed. The clinicopathologic features and results of EBER ISH and immunohistochemistry were compared according to the LNM status. Results: Among the cases, 146 EGCs (19.3 %) showed LNM. EBV negativity, larger tumor size (greater than 2 cm), deeper level of submucosal invasion, submucosal invasion depth greater than 500 µm, presence of ulceration, and presence of lymphovascular invasion (LVI) were associated with LNM. However, the MMR deficiency was not correlated with LNM. On multivariate regression analysis, larger tumor size (greater than 2 cm; odds ratio 1.6, p = 0.030), deeper level of submucosal invasion (odds ratio 2.9, p = 0.001), LVI (odds ratio 7.4, p < 0.001), and EBV negativity (p = 0.020) were independent risk factors for LNM in SM EGCs. Conclusions: EBV positivity was a favorable risk factor for LNM in SM EGC. However, MMR deficiency was not associated with the status of LNM. Thus, we suggest that examination with EBER ISH could be considered for endoscopic resected specimens, especially in cases of SM EGC showing no LVI and clear resection margins.

AB - Background: Epstein–Barr virus (EBV)-associated gastric cancer (GC) and microsatellite-instability-high GC are associated with a low prevalence of regional lymph node metastasis (LNM). To evaluate the feasibility of endoscopic treatment of EBV-associated and/or microsatellite-instability-high early GC (EGC), we analyzed the risk factors for LNM using a large series (n = 756) of submucosa-invasive (SM) EGC. Methods: EBV-encoded RNA in situ hybridization (EBER ISH) and immunohistochemistry for four mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6) were performed. The clinicopathologic features and results of EBER ISH and immunohistochemistry were compared according to the LNM status. Results: Among the cases, 146 EGCs (19.3 %) showed LNM. EBV negativity, larger tumor size (greater than 2 cm), deeper level of submucosal invasion, submucosal invasion depth greater than 500 µm, presence of ulceration, and presence of lymphovascular invasion (LVI) were associated with LNM. However, the MMR deficiency was not correlated with LNM. On multivariate regression analysis, larger tumor size (greater than 2 cm; odds ratio 1.6, p = 0.030), deeper level of submucosal invasion (odds ratio 2.9, p = 0.001), LVI (odds ratio 7.4, p < 0.001), and EBV negativity (p = 0.020) were independent risk factors for LNM in SM EGCs. Conclusions: EBV positivity was a favorable risk factor for LNM in SM EGC. However, MMR deficiency was not associated with the status of LNM. Thus, we suggest that examination with EBER ISH could be considered for endoscopic resected specimens, especially in cases of SM EGC showing no LVI and clear resection margins.

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U2 - 10.1007/s10120-015-0565-1

DO - 10.1007/s10120-015-0565-1

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AN - SCOPUS:84947093505

VL - 19

SP - 1041

EP - 1051

JO - Gastric Cancer

JF - Gastric Cancer

SN - 1436-3291

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