Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma

Abstract Gastric carcinoma with lymphoid stroma (GCLS) is characterized by dense intra-and peritumoral lymphocytic infiltration and a high rate of Epstein Barr Virus (EBV) infection, suggesting being a promising candidate for immunotherapy. We investigated correlations between PD-L1 expression and c...

Full description

Saved in:
Bibliographic Details
Main Authors: Sun Mi Lee, Hyunjoo Oh
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-81764-6
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846101171637321728
author Sun Mi Lee
Hyunjoo Oh
author_facet Sun Mi Lee
Hyunjoo Oh
author_sort Sun Mi Lee
collection DOAJ
description Abstract Gastric carcinoma with lymphoid stroma (GCLS) is characterized by dense intra-and peritumoral lymphocytic infiltration and a high rate of Epstein Barr Virus (EBV) infection, suggesting being a promising candidate for immunotherapy. We investigated correlations between PD-L1 expression and clinicopathologic factors, including EBV positivity and microsatellite instability (MSI) status in GCLSs. The study included resected 214 GCLSs and 300 gastric adenocarcinomas (GACs) for control. Epstein Barr Virus encoding region in situ hybridization (EBER ISH), immunohistochemistry for PD-L1 and HER2, dual-colored in situ hybridization for HER2, and MSI analysis were performed. EBV positivity was found in 181 (85%) of 214 GCLSs. MSI analysis demonstrated that 0.6% of EBV + GCLSs and 54.5% of EBV-GCLSs were MSI-high compared to 7% of EBV-GACs. Approximately 3% and 3.9% of HER2 amplifications were found in EBV- and EBV + GCLSs compared to 13% of EBV-GACs. PD-L1 expression with ≥ 1, ≥ 5, and ≥ 10 combined positive scores (CPS) were observed in 81.8%, 70.2%, and 55.3% of EBV + GCLSs. PD-L1 expression with ≥ 10 CPS was observed in 21.2% of EBV-GCLSs, predominantly in MSI-H tumors (85.7%). EBV positivity and MSI are associated with PD-L1 positivity rates in patients with GCLS who may respond better to PD-1/PD-L1 inhibitors but not anti-HER2 inhibitors.
format Article
id doaj-art-472ff4135e1d4712952d98aa2873f55a
institution Kabale University
issn 2045-2322
language English
publishDate 2024-12-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-472ff4135e1d4712952d98aa2873f55a2024-12-29T12:27:39ZengNature PortfolioScientific Reports2045-23222024-12-0114111010.1038/s41598-024-81764-6Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stromaSun Mi Lee0Hyunjoo Oh1Department of Pathology and Laboratory Medicine, Indiana University School of MedicineDepartment of Internal Medicine, Jeju National University HospitalAbstract Gastric carcinoma with lymphoid stroma (GCLS) is characterized by dense intra-and peritumoral lymphocytic infiltration and a high rate of Epstein Barr Virus (EBV) infection, suggesting being a promising candidate for immunotherapy. We investigated correlations between PD-L1 expression and clinicopathologic factors, including EBV positivity and microsatellite instability (MSI) status in GCLSs. The study included resected 214 GCLSs and 300 gastric adenocarcinomas (GACs) for control. Epstein Barr Virus encoding region in situ hybridization (EBER ISH), immunohistochemistry for PD-L1 and HER2, dual-colored in situ hybridization for HER2, and MSI analysis were performed. EBV positivity was found in 181 (85%) of 214 GCLSs. MSI analysis demonstrated that 0.6% of EBV + GCLSs and 54.5% of EBV-GCLSs were MSI-high compared to 7% of EBV-GACs. Approximately 3% and 3.9% of HER2 amplifications were found in EBV- and EBV + GCLSs compared to 13% of EBV-GACs. PD-L1 expression with ≥ 1, ≥ 5, and ≥ 10 combined positive scores (CPS) were observed in 81.8%, 70.2%, and 55.3% of EBV + GCLSs. PD-L1 expression with ≥ 10 CPS was observed in 21.2% of EBV-GCLSs, predominantly in MSI-H tumors (85.7%). EBV positivity and MSI are associated with PD-L1 positivity rates in patients with GCLS who may respond better to PD-1/PD-L1 inhibitors but not anti-HER2 inhibitors.https://doi.org/10.1038/s41598-024-81764-6
spellingShingle Sun Mi Lee
Hyunjoo Oh
Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma
Scientific Reports
title Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma
title_full Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma
title_fullStr Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma
title_full_unstemmed Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma
title_short Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma
title_sort association of pd l1 positivity with epstein barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma
url https://doi.org/10.1038/s41598-024-81764-6
work_keys_str_mv AT sunmilee associationofpdl1positivitywithepsteinbarrvirusinfectionandmicrosatelliteinstabilityingastriccarcinomaswithlymphoidstroma
AT hyunjoooh associationofpdl1positivitywithepsteinbarrvirusinfectionandmicrosatelliteinstabilityingastriccarcinomaswithlymphoidstroma