Retrospective Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
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 by the 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
Abstract
BACKGROUND

Anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy has demonstrated promising results on gastric cancer (GC). However, PD-L1 can express differently between metastatic sites and primary tumors (PT).

AIM

To compare PD-L1 status in PT and matched lymph node metastases (LNM) of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.

METHODS

We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy. PD-L1 was evaluated by immunohistochemistry (clone SP142) using the combined positive score. All PD-L1+ PT staged as pN+ were also tested for PD-L1 expression in their LNM. PD-L1(-) GC with pN+ served as the comparison group.

RESULTS

Among 284 GC patients included, 45 had PD-L1+ PT and 24 of them had pN+. For comparison, 44 PD-L1(-) cases with pN+ were included (sample loss of 4 cases). Of the PD-L1+ PT, 54.2% (13/24 cases) were also PD-L1+ in the LNM. Regarding PD-L1(-) PT, 9.1% (4/44) had PD-L1+ in the LNM. The agreement between PT and LNM had a kappa value of 0.483. Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites. There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status (P = 0.166 and P = 0.837, respectively).

CONCLUSION

Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM. This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Keywords: Gastric cancer, Lymph node, Programmed death ligand 1, Stomach neoplasms, Immunohistochemistry, Metastasis

Core Tip: This is a retrospective study comparing programmed death-ligand 1 (PD-L1) expression in primary tumors (PTs) and matched lymph node metastases (LNM) of gastric cancer patients who underwent D2-gastrectomy. Among 284 patients, 24 were PD-L1 positivity in PT and had LNM. 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 positive in LNM. Accordingly, the intra-patient heterogeneity in PD-L1 expression between the PT and matched LNM found in our study may emphasize the importance of considering the site of tumor sample examined when selecting patients for immunotherapy.