Akihito Kawazoe1,2,3, Takeshi Kuwata1,4, Yasutoshi Kuboki2, Kohei Shitara2, Akiko Kawano Nagatsuma1, Masaaki Aizawa5, Takayuki Yoshino2, Toshihiko Doi2, Atsushi Ohtsu2,3, Atsushi Ochiai6. 1. Division of Pathology, Research Cancer for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 2. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 3. Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan. 4. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan. 5. Department of Surgery, Niigata Cancer Center Hospital, Niigata, Niigata, Japan. 6. Division of Pathology, Research Cancer for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. aochiai@east.ncc.go.jp.
Abstract
BACKGROUND: Antibodies against programmed death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) have recently demonstrated promising results in gastric cancer (GC). PD-L1 expression, the presence of tumor-infiltrating lymphocytes (TILs), and mismatch repair (MMR) deficiency have been proposed as predictive biomarkers for anti-PD-1/PD-L1 antibodies. The aim of this study was to investigate the clinical relevance of PD-L1 expression with TIL, MMR, and Epstein-Barr virus (EBV) status in GC. METHODS: We performed a tissue microarray analysis in 487 advanced GC patients who underwent gastrectomy. PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (TIICs), the densities of TILs, and MMR status were evaluated by immunohistochemistry. EBV was detected by in situ hybridization. RESULTS: PD-L1 expression on TCs and TIICs, MMR deficiency, and EBV positivity were identified in 22.8, 61.4, 5.1, and 5.1 % cases respectively. PD-L1 expression was more frequently observed in the elderly (TCs P = 0.002), in males (TCs P = 0.029; TIICs P = 0.043), in patients with poorly differentiated adenocarcinoma with solid-type histological features (TCs P < 0.001; TIICs P < 0.001), in patients with MMR deficiency (TCs P < 0.001; TIICs P < 0.001), and in patients with EBV positivity (TCs P = 0.001; TIICs P = 0.050). Strong association was observed between PD-L1 expression and high densities of CD3-positive, CD8-positive, or forkhead box P3 positive TILs (TCs P < 0.001; TIICs P < 0.001). Neither PD-L1 expression on TCs nor that on TIICs was an independent prognostic factor in multivariate analysis. CONCLUSIONS: In GC, PD-L1 expression was associated with distinct clinicopathological features, including high densities of TILs, MMR deficiency, and EBV positivity, but was not a prognostic factor.
BACKGROUND: Antibodies against programmed death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) have recently demonstrated promising results in gastric cancer (GC). PD-L1 expression, the presence of tumor-infiltrating lymphocytes (TILs), and mismatch repair (MMR) deficiency have been proposed as predictive biomarkers for anti-PD-1/PD-L1 antibodies. The aim of this study was to investigate the clinical relevance of PD-L1 expression with TIL, MMR, and Epstein-Barr virus (EBV) status in GC. METHODS: We performed a tissue microarray analysis in 487 advanced GC patients who underwent gastrectomy. PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (TIICs), the densities of TILs, and MMR status were evaluated by immunohistochemistry. EBV was detected by in situ hybridization. RESULTS:PD-L1 expression on TCs and TIICs, MMR deficiency, and EBV positivity were identified in 22.8, 61.4, 5.1, and 5.1 % cases respectively. PD-L1 expression was more frequently observed in the elderly (TCs P = 0.002), in males (TCs P = 0.029; TIICs P = 0.043), in patients with poorly differentiated adenocarcinoma with solid-type histological features (TCs P < 0.001; TIICs P < 0.001), in patients with MMR deficiency (TCs P < 0.001; TIICs P < 0.001), and in patients with EBV positivity (TCs P = 0.001; TIICs P = 0.050). Strong association was observed between PD-L1 expression and high densities of CD3-positive, CD8-positive, or forkhead box P3 positive TILs (TCs P < 0.001; TIICs P < 0.001). Neither PD-L1 expression on TCs nor that on TIICs was an independent prognostic factor in multivariate analysis. CONCLUSIONS: In GC, PD-L1 expression was associated with distinct clinicopathological features, including high densities of TILs, MMR deficiency, and EBV positivity, but was not a prognostic factor.
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