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

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 23; no. 1; pp. 95 - 104
• Main Authors: Yamashita, Kohei, Iwatsuki, Masaaki, Harada, Kazuto, Eto, Kojiro, Hiyoshi, Yukiharu, Ishimoto, Takatsugu, Nagai, Yohei, Iwagami, Shiro, Miyamoto, Yuji, Yoshida, Naoya, Komohara, Yoshihiro, Ajani, Jaffer A., Baba, Hideo
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.01.2020; Springer Nature B.V
• Subjects: Abdominal Surgery; Aged; Apoptosis; B7-H1 Antigen - metabolism; Biomarkers; Biomarkers, Tumor - metabolism; Calcium; Calcium-Binding Proteins - metabolism; Cancer Research; Female; Gastrectomy; Gastric cancer; Gastroenterology; Humans; Immunohistochemistry; Immunohistochemistry - methods; Ligands; Lymphocytes, Tumor-Infiltrating - pathology; Macrophages; Male; Medicine; Medicine & Public Health; Microfilament Proteins - metabolism; Middle Aged; Oncology; Original Article; PD-L1 protein; Prognosis; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Stomach Neoplasms - surgery; Surgical Oncology; Survival Analysis; Tumor cells; PD-L1; Combined positive score; Gastric cancer; Prognostic biomarker
• ISSN: 1436-3291; 1436-3305; 1436-3305
• DOI: 10.1007/s10120-019-00999-9

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.