Coimbra BC, Pereira MA, Cardili L, Alves VAF, de Mello ES, Ribeiro U Jr, Ramos MFKP. Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma. World J Gastrointest Oncol 2024; 16(3): 883-893 [PMID: 38577458 DOI: 10.4251/wjgo.v16.i3.883]
Corresponding Author of This Article
Marina Alessandra Pereira, MSc, PhD, Research Scientist, Department of Gastroenterology, Instituto do Cancer, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculdade de Medicina, Universidade de São Paulo, Av Dr Arnaldo, 251, São Paulo 01246000, Brazil. marina.pereira@hc.fm.usp.br
Research Domain of This Article
Medicine, Research & Experimental
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 Gastrointest Oncol. Mar 15, 2024; 16(3): 883-893 Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.883
Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma
Brendha Cação Coimbra, Marina Alessandra Pereira, Leonardo Cardili, Venancio Avancini Ferreira Alves, Evandro Sobroza de Mello, Ulysses Ribeiro Jr, Marcus Fernando Kodama Pertille Ramos
Brendha Cação Coimbra, Marina Alessandra Pereira, Ulysses Ribeiro Jr, Marcus Fernando Kodama Pertille Ramos, Department of Gastroenterology, Instituto do Cancer, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246000, Brazil
Leonardo Cardili, Venancio Avancini Ferreira Alves, Evandro Sobroza de Mello, Department of Pathology, Instituto do Cancer, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246000, Brazil
Author contributions: Coimbra BC, Pereira MA, and Ramos MFKP contributed to the study design and data retrieval; Coimbra BC, Pereira MA, Alves VAF, Ribeiro U Jr, and Ramos MFKP were involved in the critical analysis; Coimbra BC and Pereira MA drafted the manuscript; Cardili L and de Mello ES participated in the laboratory techniques and pathological analysis; Alves VAF and Ribeiro U Jr supervised the project; Alves VAF, Ribeiro U Jr, and Ramos MFKP reviewed the manuscript; Ramos MFKP implemented the research.
Supported bythe Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP agency), 2020/02880-1.
Institutional review board statement: The study was approved by the hospital ethics committee and registered online (https://plataformabrasil.saude.gov.br; CAAE: 26380019.6.0000.0065).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marina Alessandra Pereira, MSc, PhD, Research Scientist, Department of Gastroenterology, Instituto do Cancer, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculdade de Medicina, Universidade de São Paulo, Av Dr Arnaldo, 251, São Paulo 01246000, Brazil. marina.pereira@hc.fm.usp.br
Received: December 1, 2023 Peer-review started: December 1, 2023 First decision: December 17, 2023 Revised: December 27, 2023 Accepted: January 31, 2024 Article in press: January 31, 2024 Published online: March 15, 2024 Processing time: 102 Days and 4.1 Hours
ARTICLE HIGHLIGHTS
Research background
Programmed death ligand 1 (PD-L1) expression is a potential biomarker for response to immune checkpoint inhibitors in some tumors, including in gastric cancer (GC). However, many biomarkers exhibit heterogeneity in GC, and intra-patient heterogeneity of PD-L1 expression may influence its role as predictive biomarkers.
Research motivation
Data regarding the concordance rate between PD-L1 in primary GC and matched regional lymph node metastasis (LNM) are limited.
Research objectives
This study aimed to compare PD-L1 expression in paired primary tumor (PT) and LNM from patients with GC. Clinicopathological characteristics and prognosis according to PD-L1 status were also evaluated.
Research methods
We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy. PD-L1 was evaluated by immunohistochemistry (clone SP142). PD-L1 status was defined as positive using the combined positive score ≥ 1. PD-L1+ in PT staged as pN+ were also tested for PD-L1 expression in their LNM. PD-L1(-) GC with pN+ served as the comparison group.
Research results
Among 284 patients, 24 were PD-L1 positivity in PT and had LNM. PD-L1+ in both PT and LNM were associated with larger tumor size and moderate/severe peritumoral inflammatory response. Among patients with PD-L1 positive in PT, 54.2% were also positive for PD-L1 in LNM. Considering the PD-L1 negative patients in PT, 9.1% of had PD-L1 positivity in LNM. The agreement between PT and LNM had a kappa value of 0.483 (moderate concordance). There was no difference in overall survival for PT and LNM according to the PD-L1 status.
Research conclusions
Our findings demonstrated that the expression of PD-L1 in the PT and LNM of patients with GC demonstrated discordance, and the heterogeneity observed between the sites evaluated may impact the use of PD-L1 as predictive biomarkers of response to immune checkpoint inhibitors.
Research perspectives
The intra-patient heterogeneity in PD-L1 status may emphasize the importance of considering the site of tumor sample examined when selecting patients for immunotherapy, and this difference in PD-L1 status between PT and matched LNM may be evaluated in future trials to justify the response observed in some PD-L1 negative cases in PT.
