Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance

// Jiajia Yuan 1, * , Jie Zhang 2, * , Yan Zhu 1 , Na Li 3 , Tiantian Tian 1 , Yang Li 3 , Yanyan Li 1 , Zhongwu Li 4 , Yumei Lai 4 , Jing Gao 1 , Lin Shen 1 1 Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China 2 Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China 3 Advanced Cell Diagnostics, Inc., Beijing, China 4 Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China * These authors contributed equally to this work Correspondence to: Lin Shen, email: lin100@medmail.com.cn Jing Gao, email: gaojing_pumc@163.com Keywords: programmed death-ligand-1, RNA in situ hybridization, immunohistochemistry, advanced gastric cancer Received: January 30, 2016 Accepted: April 09, 2016 Published: May 15, 2016 ABSTRACT PD-L1 expression may be a predictive marker for anti-PD-1 therapeutic efficacy. No standard detection method of PD-L1 expression was available for advanced gastric cancer (AGC), which would be investigated in this study using RNA in situ hybridization and immunohistochemistry. Patients ( N = 165) with AGC treated at Peking University Cancer Hospital from October 2008 to February 2013 were retrospectively studied. Tissue samples prior to chemotherapy were assessed for PD-L1 expression using RNA in situ hybridization (an RNAscope assay) and immunohistochemistry (IHC). The correlations of PD-L1 expression to patient characteristics and clinical outcomes were statistically analyzed. PD-L1 mRNA signals were located in tumor compartments or the mesenchyme in a brown dotted or clustered pattern, and PD-L1 mRNA expression in gastric cancer was heterogeneous. PD-L1-positive expressions were observed in 33.9% (56/165) and 35.1% (46/131) patients in mRNA level and protein level, respectively. A positive relationship was found between PD-L1 mRNA and PD-L1 protein, and compared to IHC, RNAscope assay could provide an intuitional and quantitative data with potential clinical application. No statistically significant differences occurred between PD-L1 expression and clinical response to chemotherapy, or survival. However, we found that PD-L1 expression was higher in intestinal type than in diffuse type. These findings suggested that the RNAscope assay may be a promising method for patient assessment in gastric cancer clinical trials, which would be illustrated in further study.