Abstract
BACKGROUND: The combined positive score (CPS) of the programmed death ligand-1 (PD-L1) 22C3 assay is a predictive marker of pembrolizumab monotherapy for advanced esophageal cancer (EC) patients. However, little is known about the association of the PD-L1 22C3 CPS with the clinicopathological features and heterogeneity of PD-L1 expression in EC in the Chinese population in a real-world setting. METHODS: We examined the association of the PD-L1 22C3 CPS with clinicopathological characteristics in 533 EC specimens. Further, we compared 37 cases' different blocks of the same specimen and 50 paired primary/metastatic lymph node lesions to investigate the heterogeneity of PD-L1 expression. RESULTS: PD-L1 positive expression was observed in 45.0% of 533 EC patients, including 46.8% with squamous cell carcinoma, 15.4% with adenocarcinoma, 28.6% with basaloid squamous carcinoma, 42.9% with spindle cell carcinoma, and 33.3% with neuroendocrine tumors. PD-L1 positive expression was positively associated with lymph node metastasis (59.2% chance, p = 0.021) and venous/lymphatic invasion (66.3% chance, p = 0.029). PD-L1 expression was highly consistent in different paraffin blocks of the same surgically resected specimen (concordance rate: 86.5%, p = 0.000016) and a moderate consistency (concordance rate: 78.0%, p = 0.000373) for the primary and metastatic lymph node lesion comparison. CONCLUSIONS: This is a novel study which demonstrated a positive correlation between a high PD-L1 22C3 CPS and invasion/metastasis risk in EC surgical specimens. Both paired blocks and paired primary/metastatic lymph node lesions showed significant concordance. PD-L1 heterogeneity was inferred to be mainly related to positive mononuclear inflammatory cells (MICs), which might have substantial implications for clinical practice.