Ramos MFKP, Pereira MA, de Mello ES, Cirqueira CDS, Zilberstein B, Alves VAF, Ribeiro-Junior U, Cecconello I. Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization: Analysis in western patients after curative-intent surgery. World J Clin Oncol 2021; 12(8): 688-701 [PMID: 34513602 DOI: 10.5306/wjco.v12.i8.688]
Corresponding Author of This Article
Marina Alessandra Pereira, MSc, Research Scientist, Department of Gastroenterology, Instituto do Cancer, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Av Dr Arnaldo 251, São Paulo 01249000, Brazil. marina.pereira@hc.fm.usp.br
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
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/
World J Clin Oncol. Aug 24, 2021; 12(8): 688-701 Published online Aug 24, 2021. doi: 10.5306/wjco.v12.i8.688
Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization: Analysis in western patients after curative-intent surgery
Marcus Fernando Kodama Pertille Ramos, Marina Alessandra Pereira, Evandro Sobroza de Mello, Cinthya dos Santos Cirqueira, Bruno Zilberstein, Venancio Avancini Ferreira Alves, Ulysses Ribeiro-Junior, Ivan Cecconello
Marcus Fernando Kodama Pertille Ramos, Marina Alessandra Pereira, Bruno Zilberstein, Ulysses Ribeiro-Junior, Ivan Cecconello, Department of Gastroenterology, Instituto do Cancer, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01249000, Brazil
Evandro Sobroza de Mello, Venancio Avancini Ferreira Alves, Department of Pathology, Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo 01249000, Brazil
Cinthya dos Santos Cirqueira, Department of Pathology, Instituto Adolfo Lutz, São Paulo 01246000, Brazil
Author contributions: Ramos MFKP, Pereira MA and Ribeiro-Junior U performed the study design. Ramos MFKP and Pereira MA data retrieval, critical analysis, and draft of the manuscript; De Mello ES, Cirqueira CDS, and Alves VAF performed the laboratory techniques and pathological analysis; Ribeiro-Junior U, Zilberstein B, and Cecconello I performed the critical analysis and review of the manuscript.
Supported byFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP agency), No. 2016/25524-0.
Institutional review board statement: The study was approved by the hospital ethics committee and registered online (https://plataformabrasil.saude.gov.br), No. 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 that they have no conflicts of interest that might be relevant to the contents of this manuscript.
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, Av Dr Arnaldo 251, São Paulo 01249000, Brazil. marina.pereira@hc.fm.usp.br
Received: January 27, 2021 Peer-review started: January 27, 2021 First decision: March 31, 2021 Revised: April 9, 2021 Accepted: July 23, 2021 Article in press: July 23, 2021 Published online: August 24, 2021 Processing time: 208 Days and 1.7 Hours
Abstract
BACKGROUND
Gastric cancer (GC) is a highly heterogeneous disease, and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups. However, the costs and technical complexity of molecular methodologies remains an obstacle to its adoption, and their clinical significance by other approaches needs further evidence.
AIM
To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry (IHC) and in situ hybridization (ISH).
METHODS
We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent. Microsatellite instability (MSI) status, E-cadherin, and p53 expression were analyzed by IHC, and Epstein-Barr virus (EBV) by ISH. Tissue microarrays were constructed for analysis. Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas (TCGA) Research Network Group and Asian Cancer Research Group (ACRG) classification systems.
RESULTS
A total of 287 GC patients were included. Based on IHC and ISH analysis, five profiles were defined as follows: E-cadherin aberrant (9.1%), MSI (20.9%), p53 aberrant (36.6%), EBV positivity (10.5%), and p53 normal (31%), which corresponded to tumors that showed no alteration in another profile. A flowchart according to the TCGA and ACRG classifications were used to define the subtypes, where clinical and pathological characteristics associated with GC subtypes were evidenced. Proximal location (P < 0.001), total gastrectomy (P = 0.001), and intense inflammatory infiltrate (P < 0.001) were characteristics related to EBV subtype. MSI subtype was predominantly associated with advanced age (P = 0.017) and the presence of comorbidities (P = 0.011). While Laurén diffuse type (P < 0.001) and advanced stage (P = 0.029) were related to genomically stable (GS) subtype. GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival (DFS) and overall survival (OS) than other subtypes. Conversely, MSI subtype of GC had better survival in both classifications. Type of gastrectomy, pT and the TCGA subtypes were independent factors associated to DFS and OS.
CONCLUSION
The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis, resembling the subtypes of the molecular classifications. Accordingly, this method of classification may represent a viable option for use in a clinical setting.
Core Tip: In this study, patients with gastric cancer (GC) were retrospectively evaluated based on subgroups of molecular classification by immunohistochemistry and in situ hybridization. Microsatellite instability status, e-cadherin, p53 expression, and Epstein-Barr virus were evaluated in a Western cohort of GC patients treated with curative intent, where it was possible to obtain subgroups with different clinicopathological characteristics and prognosis. Thus, our findings demonstrate that through techniques used in the routine pathological evaluation it is possible to identify immunophenotypic groups of GC similar to those determined by the molecular classification.
