Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2017; 23(40): 7292-7302
Published online Oct 28, 2017. doi: 10.3748/wjg.v23.i40.7292
Clinical and pathological characterization of Epstein-Barr virus-associated gastric carcinomas in Portugal
Joana Ribeiro, Andreia Oliveira, Mariana Malta, Claudia Oliveira, Fernanda Silva, Ana Galaghar, Luís Pedro Afonso, Maria Cassiano Neves, Rui Medeiros, Pedro Pimentel-Nunes, Hugo Sousa
Joana Ribeiro, Andreia Oliveira, Mariana Malta, Claudia Oliveira, Rui Medeiros, Hugo Sousa, Molecular Oncology and Viral Pathology Group, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
Joana Ribeiro, Faculty of Medicine of Porto University, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Fernanda Silva, Ana Galaghar, Luís Pedro Afonso, Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
Maria Cassiano Neves, Medical Oncology Department, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
Maria Cassiano Neves, Instituto CUF de Oncologia, Rua Mário Botas, 1998-018 Lisbon, Portugal
Rui Medeiros, Hugo Sousa, Virology Service, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
Rui Medeiros, Research Department - Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro - Núcleo Regional do Norte), Estrada Interior da Circunvalação nº 6657, 4200- 172 Porto, Portugal
Pedro Pimentel-Nunes, Gastroenterology Service, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
Pedro Pimentel-Nunes, CINTESIS - Center for Health Technology and Services Research (Centro de Investigação Médica, Faculdade de Medicina da Universidade do Porto), Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal
Author contributions: Ribeiro J, Oliveira A, Malta M and Oliveira C performed the laboratory of experiments; Silva F and Galaghar A were responsible for the histological sectional selection; Galaghar A and Afonso LP revised the histological classification; Neves MC and Ribeiro J revised all clinical data; Medeiros R and Pimentel-Nunes P supervised the research and clinical data, respectively; Ribeiro J and Sousa H designed the study and performed the data analysis; Sousa H coordinated the study; Ribeiro J and Sousa H prepared the manuscript; all authors revised and collaborated in the manuscript writing and final preparation.
Supported by this article was supported by FEDER through the operation POCI-01-0145-FEDER-007746 funded by the Programa Operacional Competitividade e Internacionalização – COMPETE2020 and by National Funds through FCT - Fundação para a Ciência e a Tecnologia within CINTESIS, R&D Unit (reference UID/IC/4255/2013). Joana Ribeiro has been granted with a PhD Scholarship (SFRH/BD/107740/2015) from FCT - Fundação para Ciência e Tecnologia.
Institutional review board statement: All procedures were approved by the Ethical Committee of IPO Porto (CES IPO 80/2014).
Informed consent statement: Patients were not required to give informed consent to this study. The study included samples from the institution tumour bank of patients with cancer after each patient agreed to treatment by written consent.
Conflict-of-interest statement: Authors declare no conflict of interests in the reported study.
Data sharing statement: Data will be provided upon request to corresponding author.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hugo Sousa, MD, PhD, Grupo de Oncologia Molecular e Patologia Viral, Laboratórios 4º Piso, Instituto Português de Oncologia do Porto FG EPE, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal. hugo.sousa@ipoporto.min-saude.pt
Telephone: +351-225-084000-5410 Fax: +351-225-084001
Received: June 8, 2017
Peer-review started: June 8, 2017
First decision: July 10, 2017
Revised: July 27, 2017
Accepted: August 15, 2017
Article in press: August 15, 2017
Published online: October 28, 2017
Abstract
AIM

To determine the prevalence of Epstein-Barr virus (EBV)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics.

METHODS

We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer (GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. EBV was detected by in situ hybridization for the detection of EBV-encoded small RNAs (EBERs) and EBV latent proteins (LMP1 and LMP2A) were detected by immunohistochemistry.

RESULTS

The analysis showed that EBV-associated gastric carcinomas (EBVaGC) represents 8.4% (15/179) of all GC cases, with a significant differential distribution among histological types (P < 0.001): 100% (3/3) of medullary carcinomas, 100% (1/1) of adenosquamous carcinoma, 8.7% (8/92) of tubular adenocarcinomas, 8.0% (2/25) of mixed carcinomas and 2% (1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of EBVaGC in the upper third and middle (cardia, fundus and body) of the stomach (P = 0.041), a significant lower number of regional lymph nodes invasion (P = 0.025) and a tendency for better prognosis (P = 0.222). EBV latent protein expression revealed that all EBVaGC cases were LMP1-negative, nevertheless 6 cases (40%) expressed LPM2A, which reveals that these cases show a distinct EBV-Latency profile (latency II-like).

CONCLUSION

EBVaGC represents 8.4% of all GC in the North Region of Portugal. The EBV-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.

Keywords: Gastric cancer, Epstein-Barr virus, Prevalencel, Epstein-Barr virus-associated gastric carcinomas

Core tip: This is the first study to report the prevalence of Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGC) in Portugal. The EBVaGCs were found in 8.4% of all gastric cancer cases, being more frequent in upper and middle regions of the stomach and among tubular and medullary carcinomas. Patients with EBV-positive tumours also have a significant lower number of regional lymph nodes with metastasis and a tendency for a better prognosis.