Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.883
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
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.
Data regarding the concordance rate between PD-L1 in primary GC and matched regional lymph node metastasis (LNM) are limited.
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.
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.
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.
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.
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.