EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement

Josine van Beek, Axel zur Hausen, Elma Klein Kranenbarg, Cornelis J H van de Velde, Jaap M Middeldorp, Adriaan J C van den Brule, Chris J L M Meijer, Elisabeth Bloemena

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: Epstein-Barr virus (EBV) is detected in a substantial subgroup of gastric adenocarcinomas worldwide. We have previously reported that these EBV-positive gastric carcinomas carry distinct genomic aberrations. In the present study, we analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features to determine whether they constitute a different clinical entity.

PATIENTS AND METHODS: Using a validated polymerase chain reaction/enzyme immunoassay-based prescreening method in combination with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor cells of 7.2% (n = 41) of the gastric carcinomas from the Dutch D1D2 trial (N = 566; mean follow-up, 9 years). EBV status was correlated with clinicopathologic features collected for the Dutch D1D2 trial.

RESULTS: EBV-positive gastric carcinomas occurred significantly more frequently in males (P <.0001) and in younger patients (P =.012). Most were of the intestinal type according to the Laurén classification (P =.047) or tubular according to the WHO classification (P =.006) and located in the proximal part of the stomach (P <.0001). A significantly lower tumor-node-metastasis system-stage (P =.026) was observed in the patients with EBV-carrying carcinomas, which was solely explained by less lymph node (LN) involvement (P =.034) in these cases. In addition, a better prognosis, as reflected by a longer disease-free period (P =.04) and a significant better cancer-related survival (P =.02), was observed for these patients, which could be explained by less LN involvement, less residual disease, and younger patient age.

CONCLUSION: EBV-carrying gastric adenocarcinomas are a distinct entity of carcinomas, characterized not only by unique genomic aberrations, but also by distinct clinicopathologic features associated with significantly better prognosis.

Original languageEnglish
Pages (from-to)664-70
Number of pages7
JournalJournal of Clinical Oncology
Volume22
Issue number4
DOIs
Publication statusPublished - 15 Feb 2004

Cite this

van Beek, Josine ; zur Hausen, Axel ; Klein Kranenbarg, Elma ; van de Velde, Cornelis J H ; Middeldorp, Jaap M ; van den Brule, Adriaan J C ; Meijer, Chris J L M ; Bloemena, Elisabeth. / EBV-positive gastric adenocarcinomas : a distinct clinicopathologic entity with a low frequency of lymph node involvement. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 4. pp. 664-70.
@article{3a940ae1e6ae458fbe643f0d114eac4e,
title = "EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement",
abstract = "PURPOSE: Epstein-Barr virus (EBV) is detected in a substantial subgroup of gastric adenocarcinomas worldwide. We have previously reported that these EBV-positive gastric carcinomas carry distinct genomic aberrations. In the present study, we analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features to determine whether they constitute a different clinical entity.PATIENTS AND METHODS: Using a validated polymerase chain reaction/enzyme immunoassay-based prescreening method in combination with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor cells of 7.2{\%} (n = 41) of the gastric carcinomas from the Dutch D1D2 trial (N = 566; mean follow-up, 9 years). EBV status was correlated with clinicopathologic features collected for the Dutch D1D2 trial.RESULTS: EBV-positive gastric carcinomas occurred significantly more frequently in males (P <.0001) and in younger patients (P =.012). Most were of the intestinal type according to the Laur{\'e}n classification (P =.047) or tubular according to the WHO classification (P =.006) and located in the proximal part of the stomach (P <.0001). A significantly lower tumor-node-metastasis system-stage (P =.026) was observed in the patients with EBV-carrying carcinomas, which was solely explained by less lymph node (LN) involvement (P =.034) in these cases. In addition, a better prognosis, as reflected by a longer disease-free period (P =.04) and a significant better cancer-related survival (P =.02), was observed for these patients, which could be explained by less LN involvement, less residual disease, and younger patient age.CONCLUSION: EBV-carrying gastric adenocarcinomas are a distinct entity of carcinomas, characterized not only by unique genomic aberrations, but also by distinct clinicopathologic features associated with significantly better prognosis.",
keywords = "Adenocarcinoma, Cohort Studies, Disease-Free Survival, Epstein-Barr Virus Infections, Female, Humans, In Situ Hybridization, Male, Middle Aged, Netherlands, Prevalence, Proportional Hazards Models, Stomach Neoplasms, Survival Analysis, Survival Rate, Journal Article, Research Support, Non-U.S. Gov't",
author = "{van Beek}, Josine and {zur Hausen}, Axel and {Klein Kranenbarg}, Elma and {van de Velde}, {Cornelis J H} and Middeldorp, {Jaap M} and {van den Brule}, {Adriaan J C} and Meijer, {Chris J L M} and Elisabeth Bloemena",
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EBV-positive gastric adenocarcinomas : a distinct clinicopathologic entity with a low frequency of lymph node involvement. / van Beek, Josine; zur Hausen, Axel; Klein Kranenbarg, Elma; van de Velde, Cornelis J H; Middeldorp, Jaap M; van den Brule, Adriaan J C; Meijer, Chris J L M; Bloemena, Elisabeth.

In: Journal of Clinical Oncology, Vol. 22, No. 4, 15.02.2004, p. 664-70.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - EBV-positive gastric adenocarcinomas

T2 - a distinct clinicopathologic entity with a low frequency of lymph node involvement

AU - van Beek, Josine

AU - zur Hausen, Axel

AU - Klein Kranenbarg, Elma

AU - van de Velde, Cornelis J H

AU - Middeldorp, Jaap M

AU - van den Brule, Adriaan J C

AU - Meijer, Chris J L M

AU - Bloemena, Elisabeth

PY - 2004/2/15

Y1 - 2004/2/15

N2 - PURPOSE: Epstein-Barr virus (EBV) is detected in a substantial subgroup of gastric adenocarcinomas worldwide. We have previously reported that these EBV-positive gastric carcinomas carry distinct genomic aberrations. In the present study, we analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features to determine whether they constitute a different clinical entity.PATIENTS AND METHODS: Using a validated polymerase chain reaction/enzyme immunoassay-based prescreening method in combination with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor cells of 7.2% (n = 41) of the gastric carcinomas from the Dutch D1D2 trial (N = 566; mean follow-up, 9 years). EBV status was correlated with clinicopathologic features collected for the Dutch D1D2 trial.RESULTS: EBV-positive gastric carcinomas occurred significantly more frequently in males (P <.0001) and in younger patients (P =.012). Most were of the intestinal type according to the Laurén classification (P =.047) or tubular according to the WHO classification (P =.006) and located in the proximal part of the stomach (P <.0001). A significantly lower tumor-node-metastasis system-stage (P =.026) was observed in the patients with EBV-carrying carcinomas, which was solely explained by less lymph node (LN) involvement (P =.034) in these cases. In addition, a better prognosis, as reflected by a longer disease-free period (P =.04) and a significant better cancer-related survival (P =.02), was observed for these patients, which could be explained by less LN involvement, less residual disease, and younger patient age.CONCLUSION: EBV-carrying gastric adenocarcinomas are a distinct entity of carcinomas, characterized not only by unique genomic aberrations, but also by distinct clinicopathologic features associated with significantly better prognosis.

AB - PURPOSE: Epstein-Barr virus (EBV) is detected in a substantial subgroup of gastric adenocarcinomas worldwide. We have previously reported that these EBV-positive gastric carcinomas carry distinct genomic aberrations. In the present study, we analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features to determine whether they constitute a different clinical entity.PATIENTS AND METHODS: Using a validated polymerase chain reaction/enzyme immunoassay-based prescreening method in combination with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor cells of 7.2% (n = 41) of the gastric carcinomas from the Dutch D1D2 trial (N = 566; mean follow-up, 9 years). EBV status was correlated with clinicopathologic features collected for the Dutch D1D2 trial.RESULTS: EBV-positive gastric carcinomas occurred significantly more frequently in males (P <.0001) and in younger patients (P =.012). Most were of the intestinal type according to the Laurén classification (P =.047) or tubular according to the WHO classification (P =.006) and located in the proximal part of the stomach (P <.0001). A significantly lower tumor-node-metastasis system-stage (P =.026) was observed in the patients with EBV-carrying carcinomas, which was solely explained by less lymph node (LN) involvement (P =.034) in these cases. In addition, a better prognosis, as reflected by a longer disease-free period (P =.04) and a significant better cancer-related survival (P =.02), was observed for these patients, which could be explained by less LN involvement, less residual disease, and younger patient age.CONCLUSION: EBV-carrying gastric adenocarcinomas are a distinct entity of carcinomas, characterized not only by unique genomic aberrations, but also by distinct clinicopathologic features associated with significantly better prognosis.

KW - Adenocarcinoma

KW - Cohort Studies

KW - Disease-Free Survival

KW - Epstein-Barr Virus Infections

KW - Female

KW - Humans

KW - In Situ Hybridization

KW - Male

KW - Middle Aged

KW - Netherlands

KW - Prevalence

KW - Proportional Hazards Models

KW - Stomach Neoplasms

KW - Survival Analysis

KW - Survival Rate

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1200/JCO.2004.08.061

DO - 10.1200/JCO.2004.08.061

M3 - Article

VL - 22

SP - 664

EP - 670

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 4

ER -