Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2021; 13(4): 265-278
Published online Apr 15, 2021. doi: 10.4251/wjgo.v13.i4.265
Expression profiles of gastric cancer molecular subtypes in remnant tumors
Marcus Fernando Kodama Pertille Ramos, Marina Alessandra Pereira, Leonardo Cardili, Evandro Sobroza de Mello, Ulysses Ribeiro Jr, Bruno Zilberstein, Ivan Cecconello
Marcus Fernando Kodama Pertille Ramos, Marina Alessandra Pereira, Ulysses Ribeiro Jr, Bruno Zilberstein, Ivan Cecconello, Department of Gastroenterology, Instituto do Cancer, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01249000, São Paulo, Brazil
Leonardo Cardili, Evandro Sobroza de Mello, Department of Pathology, Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01249000, São Paulo, Brazil
Author contributions: Ramos MFKP and Pereira MA contributed to study design, data retrieval, critical analysis, and draft of the manuscript; Cardili L and de Mello ES contributed to data retrieval and pathological analysis; Ribeiro Jr U, Zilberstein B and Cecconello I contributed to critical analysis and review of the manuscript.
Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, No. 2016/25524-0.
Institutional review board statement: The study was approved by the Hospital das Clínicas da Faculdade de Medicina da USP Ethics Committee and registered online (https://plataformabrasil.saude.gov.br; CAAE: 37009120.0.0000.0068).
Informed consent statement: Informed consent was waived by the local Ethics Committee because of the retrospective nature of the study.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Marina Alessandra Pereira, MSc, Research Scientist, Department of Gastroenterology, Instituto do Cancer, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, 251 Av Dr Arnaldo, São Paulo 01249000, São Paulo, Brazil. marina.pereira@hc.fm.usp.br
Received: December 23, 2020
Peer-review started: December 23, 2020
First decision: February 14, 2021
Revised: February 16, 2021
Accepted: March 22, 2021
Article in press: March 22, 2021
Published online: April 15, 2021
Processing time: 106 Days and 23.9 Hours
Abstract
BACKGROUND

Remnant gastric cancer (RGC) is a carcinoma arising in the stomach remnant after previous gastric resection. It is frequently reported as a tumor with a poor prognosis and distinct biological features from primary gastric cancer (PGC). However, as it is less frequent, its profile regarding the current molecular classifications of gastric cancer has not been evaluated.

AIM

To evaluate a cohort of RGC according to molecular subtypes of GC using a panel of immunohistochemistry and in situ hybridization to determine whether the expression profile is different between PGC and RGC.

METHODS

Consecutive RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using seven GC panels: Epstein-Barr virus in situ hybridization, immunohistochemistry for mismatch repair proteins (MutL homolog 1, MutS homolog 2, MutS homolog 6, and PMS1 homolog 2), p53 protein, and E-cadherin expression. Clinicopathological characteristics and survival of these patients were compared to 284 PGC patients.

RESULTS

A total of 40 RGC patients were enrolled in this study. Compared to PGC, older age (P < 0.001), male (P < 0.001), lower body mass index (P = 0.010), and lower hemoglobin level (P < 0.001) were associated with RGC patients. No difference was observed regarding Lauren’s type and pathologic Tumor Node Metastasis stage between the groups. Regarding the profiles evaluated, EBV-positive tumors were higher in RGC compared to PGC (P = 0.039). The frequency of microsatellite instability, aberrant p53 immunostaining, and loss of E-cadherin expression were similar between RGC and PGC. Higher rates of simultaneous alterations in two or more profiles were observed in RGC compared to PGC (P < 0.001). According to the molecular classification, the subtypes were defined as EBV in nine (22.5%) cases, microsatellite instability in nine (22.5%) cases, genomically stable in one (2.5%) case, and chromosomal instability in 21 (52.5%) cases. There was no significant difference in survival between molecular subtypes in RGC patients.

CONCLUSION

RGC was associated with EBV positivity and higher rates of co-altered expression profiles compared to PGC. According to the molecular classification, there was no significant difference in survival between the subtypes of RGC.

Keywords: Stomach neoplasms; Gastric remnant; Gastric remnant cancer; Adenocarcinoma; Immunohistochemistry

Core Tip: This is a retrospective study to evaluate the molecular subtypes of gastric cancer (GC) using a panel by immunohistochemistry and in situ hybridization in remnant GC (RGC). We also compared the RGC patients with primary GC (PGC) to investigate whether the expression profiles were different between both types of GC. The findings indicated that RGC was associated with the Epstein-Barr virus. RGC also exhibited higher rates of simultaneous changes in two or more profiles compared to PGC. However, molecular subtypes of GC had no significant prognostic impact in terms of survival in RGC patients.