Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.

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