Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance
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Jiajia Yuan1,*, Jie Zhang2,*, Yan Zhu1, Na Li3, Tiantian Tian1, Yang Li3, Yanyan Li1, Zhongwu Li4, Yumei Lai4, Jing Gao1, Lin Shen1
1Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
2Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
3Advanced Cell Diagnostics, Inc., Beijing, China
4Department 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
Lin Shen, email: email@example.com
Jing Gao, email: firstname.lastname@example.org
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
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.
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