Abstract 4717: Combination of PD-L1 expression and microsatellite instability status is a useful prognostic factor in gastric cancer
Authors: Toshiaki Morihiro, Shinji Kuroda, Nobuhiko Kanaya, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara
Journal: Cancer Research (2017)

Abstract Interaction of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) induces functional impairment of antigen-specific T cells, which leads to immune evasion of tumors. Immune checkpoint therapy including PD-1/PD-L1 blockade is an emerging treatment strategy which brings great improvement in patient’s prognosis. Microsatellite instability (MSI) is a condition of genomic instability caused by the loss of DNA mismatch repair activity, which has recently received a lot of attention from the standpoint of cancer immunotherapy. While the TNM classification system is commonly used on various malignant tumors for prediction of prognosis and planning of treatment strategy, establishment of prognostic factors related to cancer immune system is considered important as cancer immunotherapy has recently become more and more popular. Thus, we investigated the usefulness of PD-L1 expression and MSI status in addition to histological type as prognostic factors in gastric cancer. In this study, 255 gastric cancer cases which had curative surgical resection at Okayama University Hospital between 2002 and 2009 were analyzed retrospectively. PD-L1 expression level was classified into 4 groups according to PD-L1 positive rate on tumors on immunohistochemical staining (0: &amp;lt; 1%, 1+: 1-5%, 2+: 5-10%, 3+: ≥10%), and 2+ and 3+ were defined as PD-L1 positive. MSI status was analyzed by PCR and classified into MSI-high (MSI-H), and MSI-low and Microsatellite stability (non-MSI). Histological type was divided into intestinal and diffuse according to the Lauren classification.PD-L1 positive rate was 15%, and PD-L1 positive was significantly correlated with advanced stage and invasive status. Overall survival (p=0.0109) and disease-free survival (p=0.0052) were significantly poor in PD-L1 positive group, and a multivariate analysis revealed that PD-L1 expression was an independent risk factor for recurrence after surgery (p=0.0160, odds ratio: 3.19). MSI-H was detected in 7.5%, and more observed in PD-L1 positive cases (p=0.0068). Although non-MSI, as a single factor, showed only a weak tendency to have poor prognosis compared to MSI-H (p=0.1965), combination of PD-L1 positive and non-MSI (PD-L1/non-MSI) showed significantly poor prognosis (p=0.0010). Although other combinations also showed the usefulness in detection of patients with poor prognosis, such as PD-L1 positive and diffuse type, and non-MSI and diffuse type, a multivariate analysis revealed that PD-L1/non-MSI was the most useful combination among them to predict poor prognosis (p=0.0009, hazard ratio: 3.88). In conclusion, while PD-L1 expression is a useful prognostic factor and predictive factor for recurrence after surgery as a single factor, combination with MSI status can be more useful and attractive prognostic factor in gastric cancer. Citation Format: Toshiaki Morihiro, Shinji Kuroda, Nobuhiko Kanaya, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara. Combination of PD-L1 expression and microsatellite instability status is a useful prognostic factor in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4717. doi:10.1158/1538-7445.AM2017-4717