Loss of epithelial membrane protein-2 expression confers an independent prognosticator in gallbladder carcinoma

The objective of this study was to evaluate the expression of epithelial membrane protein-2 (EMP2) and its clinicopathological associations in patients with gallbladder carcinoma (GBC). A retrospective population-based cohort study was performed based on a biobank from 1986 to 2005. Biopsies of 164 GBC patients without initial distant metastasis were collected during surgical intervention. Immunoexpressions of EMP2 and Ki-67 were analyzed and the outcomes were correlated with clinicopathological features and patient survival. Results indicated that loss of EMP2 expression (50%) was correlated with female patients (p = 0.037), advanced primary tumor (p < 0.017), vascular (p < 0.001), and perineural (p < 0.027) invasions and high Ki-67 labeling index (p < 0.001).In multivariate analysis, loss of EMP2 expression, high Ki-67 labeling index, and age emerged as independent prognosticators for worse disease-specific (p < 0.001; p < 0.001; and p = 0.001, respectively) and disease-free (p = 0.002; p = 0.002; and p = 0.008, respectively) survivals, following by the American Joint Committee on Cancer stage (p < 0.001; p < 0.001; and p < 0.001, respectively). Collectively, loss of EMP2 expression is common and associated with adverse prognosticators and might confer tumor aggressiveness through hampering its interaction with specific membrane protein(s) and antiproliferative activity, and perhaps the downstream signal transduction pathway(s).