Prognostic impacts of the combined positive score and the tumor proportion score for programmed death ligand-1 expression by double immunohistochemical staining in patients with advanced gastric cancer

摘要

Background The tumor proportion score (TPS) and combined positive score (CPS) have been developed to assess programmed death ligand 1 (PD-L1) expression in gastric cancer (GC). This study aimed to elucidate the role of TPS and CPS as prognostic biomarkers. Methods A total of 191 patients with GC who received curative gastrectomy were retrospectively enrolled. Double immunohistochemistry of PD-L1 and ionized calcium binding adaptor molecule 1 was performed to clearly distinguish PD-L1 expression between tumor cells and macrophages. Survival analysis for PD-L1 expression by TPS and CPS was performed. Results PD-L1 positivity was detected in 39 patients (20.4%) by TPS and in 137 patients (71.7%) by CPS. Patients with PD-L1 positivity by CPS experienced significantly shorter overall survival (OS) (P < 0.01) and relapse-free survival (RFS) (P = 0.01) than the other patients. In contrast, patients with either PD-L1 status by the TPS showed similar OS and RFS times. Multivariate Cox regression analysis for OS and RFS demonstrated that PD-L1 positivity by CPS was a significant independent factor for poor OS (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.27-4.37, P < 0.01) and RFS (HR 1.81, 95% CI 1.07-3.22, P = 0.03). Conclusions CPS was shown to be a more useful assessment method of determining PD-L1 expression than TPS as a prognostic biomarker. This suggests that the total number of PD-L1-expressing cells, including tumor and immune cells, is a more sensitive prognostic biomarker than the number of PD-L1-expressing tumor cells in GC.