Expression profiles of gastric cancer molecular subtypes in remnant tumors

doi:10.4251/wjgo.v13.i4.265

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World Journal of Gastrointestinal Oncology

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Retrospective Study

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.

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

ARTICLE HIGHLIGHTS

Research background

Remnant gastric cancer (RGC) is defined as a carcinoma arising in the stomach remnant after a previous gastrectomy. Despite the improvement in diagnosis and treatment, difficulties in predicting the prognosis and the best therapeutic approach in RGC patients are still challenges in clinical practice.

Research motivation

New classifications based on molecular subtypes have provided a promising prognostic tool and facilitate the development of targeted agents in clinical trials. However, gastric cancer (GC) profiles and the distribution of molecular subtypes have not been evaluated for RGC.

Research objectives

This study aimed to evaluate RGC according to molecular subtypes and determine whether the expression profile is different between RGC and primary GC (PGC).

Research methods

RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using a panel of immunohistochemistry (IHC) and in situ hybridization (ISH): Epstein-Barr virus (EBV) ISH, IHC for mismatch repair proteins (MutL homolog 1, MutS homolog 2, MutS homolog 6, and PMS1 homolog 2), p53 protein, and E-cadherin expression.

Research results

A total of 40 RGC patients were included, and 284 PGC served as a comparison group. 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 changes in two or more profiles were observed in RGC compared to PGC. According to the molecular classification, there was no significant difference in survival between the subtypes of RGC.

Research conclusions

The presence of EBV-positive was significantly higher in patients with RGC compared to PGC. In addition, they also exhibited higher rates of co-altered expression profile profiles compared to PGC.

Research perspectives

Our findings provide new data regarding the profiles of RGC according to the subtypes of molecular classification, reflecting potential differences from PGC that may assist in determining which markers could best define GC subtypes and stratify patients with RGC to the appropriate screening and treatment programs.