Ezrin Expression Is an Independent Prognostic Factor in Gastro-intestinal Cancers

Abstract

BackgroundEzrin, a member of the ezrin–radixin–moesin (ERM) family of plasma membrane–cytoskeleton linker proteins, has been associated with metastatic behavior. MethodologyMicroarrayed pathological tissues of surgically resected colorectal cancer liver metastasis (CRLM) and whole tissue sections of cancer of the ampulla of Vater (CAV) were analyzed to determine ezrin expression levels and correlation with survival. The requirement of ezrin in invasive capability was assessed using in vitro assays. ResultsSurgically resected CAV showing a low ezrin score have a better 5-year disease-specific survival than those showing a high ezrin score (P < 0.0001). Similarly, high ezrin expression at the invasive front of CRLM resulted in poor disease-free survival (P = 0.05). Multivariate analysis demonstrated high ezrin expression to be an independent adverse prognostic factor for CAV (hazard ratio (HR) 15.22 (95 % confidence interval (CI) 1.98–117.03), P < 0.01) and CRLM (HR 6.42 (95 % CI 1.01–52.43), P = 0.05), among other clinically relevant variables such as lymph node metastasis (for CAV) and the presence of extrahepatic disease, large hepatic metastases (>5 cm), and close surgical resection margins (<5 mm) (all for CRLM). In vitro experiments indicated that ezrin expression was vital for cellular processes such as adhesive and invasive activity. SignificanceHigh ezrin expression indicates an adverse prognosis in primary CAV and CRLM.