Concordance of PD-L1 status in primary gastroesophageal adenocarcinoma and matched peritoneal metastases: a single institution study

Abstract

Background: Programmed death-ligand 1 (PD-L1) expression serves as a predictive biomarker for response to immune checkpoint inhibitors (ICIs) in metastatic gastroesophageal adenocarcinoma (mGEA). The peritoneum is one of the most common metastatic sites and is associated with a poor prognosis and apparently lower clinical efficacy of ICIs. Patients and methods: We investigated the heterogeneity of PD-L1 expression in mGEA by examining its concordance between primary tumors and matched peritoneal metastases (PMs), and before and after systemic treatment. PD-L1 expression was assessed using combined positive score (CPS) by immunohistochemistry with VENTANA PD-L1 (SP263) assays on formalin-fixed paraffin-embedded tumor tissues. Results were reported using CPS cut-offs of 1 and 5. Results: Twenty-two primary tumor and matched PM specimens from patients with mGEA were analyzed. The concordance of PD-L1 CPS was 54.5% with a CPS cut-off of 1 and 72.7% with a CPS cut-off of 5, highlighting spatial heterogeneity. Notably, none of the PD-L1-positive primary tumor samples tested positive in the matched PM specimens using the CPS ≥5 cut-off. Potential temporal heterogeneity of PD-L1 expression related to chemo(immuno)therapy administration was also observed, with a 55.6% concordance rate using the CPS ≥5 cut-off. Conclusions: PD-L1 expression in PMs from mGEA is characterized by both spatial and potentially temporal heterogeneity, with the variability being more pronounced at lower CPS cut-off values. This variability complicates its role as a predictive biomarker for ICI outcomes. The high intrapatient discordance rate in PD-L1 CPS expression between positive primary tumor samples and matched PM specimens suggests that peritoneal specimens should not be used as the only source for PD-L1 assessment if representative tissue from other disease sites is available.

Keywords

• gastroesophageal adenocarcinoma
• peritoneal metastases
• PD-L1
• combined positive score
• heterogeneity