1994P - Low LATS2 expression is associated with poor prognosis in non small cell lung cancer

Large tumor suppressor kinase 2 (LATS2) is one of the core components in the Hippo signaling pathway, and it functions as a tumor suppressor associated with regulating tumor cell proliferation and apoptosis. Dysregulated LATS2 expression has been reported in various human cancers. The purpose of this study is to explore LATS2 expression and its clinicopathological significance in non-small cell lung cancer (NSCLC) and its subtypes. We examined LATS2 protein expression by immunohistochemistry in 184 resected NSCLC specimens on tissue microarray. We also reviewed the clinical data and performed a clinicopathological analysis. Of 184 lung cancer specimens, 40 (21.7%) showed low LATS2 expression. Low LATS2 expression was significantly correlated with disease recurrence (p=0.047) and low LATS2 expression had a tendency of poor prognostic clinicopathological features including large tumor size, the presence of vascular and lymphatic invasion and distant metastasis. The low LATS2 expression group showed a statistically poorer overall survival (OS) (p=0.004) and disease-free survival (DFS) (p=0.014) than did the high expression group in Kaplan-Meier analysis with log-rank test. In multivariate analysis with the Cox proportional hazards model, downregulated LATS2 expression in NSCLC was an independent prognostic factor of poor OS and DFS. Furthermore, we evaluated the prognostic significance of LATS2 expression in two major subtypes of NSCLC, squamous cell carcinoma and adenocarcinoma, using the Kaplan-Meier curves with log-rank test. In both squamous cell carcinoma and adenocarcinoma, low LATS2 expression group showed worse prognosis than high LATS2 expression group (OS (p=0.144), DFS (p=0.022) in squamous cell carcinoma and OS (p=0.045), DFS (p=0.271) in adenocarcinoma). In conclusion, we demonstrated that downregulated LATS2 expression may predict aggressive biologic behavior and a worse prognosis in NSCLC and we also suggested the possibility of LATS2 as a therapeutic target in both squamous cell carcinoma and adenocarcinoma of the lung. The authors. Soonchunhyang University Research Fund. All authors have declared no conflicts of interest.