BRMS1 and HPA as Progression, Clinical Biological Behaviors, and Poor Prognosis-related Biomarkers for Gallbladder Adenocarcinoma.

PURPOSE: To study the expression of breast cancer metastasis suppressor 1 (BRMS1) and heparanase (HPA) and evaluate their clinicopathologic significance and relationship in benign and malignant lesions of the gallbladder. MATERIALS AND METHODS: EnVision immunohistochemical method for determining the expression of BRMS1 and HPA was used in routinely paraffin-embedded sections of surgical resected specimens from gallbladder adenocarcinoma, peritumoral tissues, polyp, and chronic cholecystitis. RESULTS: The positive rate of BRMS1 expression was significantly lower in gallbladder adenocarcinoma than that in peritumoral tissues (P<0.01), polyp (P<0.01), and chronic cholecystitis (P<0.01). The positive rate of HPA expression was significantly higher in gallbladder adenocarcinoma than that in peritumoral tissues (P<0.01), polyp (P<0.05), and chronic cholecystitis (P<0.01). The positive expression of BRMS1 and negative expression of HPA were significantly associated with differentiation, lymph node metastasis, and invasion of adenocarcinoma (P<0.05 or P<0.01). Unitivariate Kaplan-Meier analysis showed that decreased expression of BRMS1 (P=0.008) or increased expression of HPA (P=0.016) was associated with decreased overall survival. Multivariate Cox regression analysis showed that decreased expression of BRMS1 (P=0.011) and/or increased expression of HPA (P=0.019) was an independent bad prognostic predictor in gallbladder adenocarcinoma. CONCLUSION: The expression of BRMS1 and/or HPA might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.