Clinicopathologic correlation of autophagy-related Beclin-1 expression in gallbladder cancer.

BACKGROUND/AIMS: Autophagy plays critical roles in both cell survival and cell death. Beclin-1, a key modulator of autophagy function, is considered a haploinsufficient tumor suppressor. The role of Beclin-1 expression in cancer is still controversial. Some studies favor the idea that autophagy suppresses tumor development, whereas other researchers suggest that autophagy enhances tumorigenesis. The expression and function of Beclin-1 in gallbladder cancer (GBCA) remain largely unknown. METHODOLOGY: Methodology: We performed immunohistochemical staining for Beclin-1 in 119 GBCA cases, and investigated whether Beclin-1 expression correlated with clinicopathologic characteristics and prognosis of patients. RESULTS: Beclin-1 was expressed in the cytoplasm of cancer cells with occasional nuclear staining in 53 (44.5%) of the 119 cases of GBCA with no expression in adjacent normal epithelial cells. Increased expression of Beclin-1 was significantly associated with longer survival rate of patients with GBCA in univariate (p=0.006) and multivariate analyses (p=0.005). There is no association between Beclin-1 expression and clinicopathologic characteristics. CONCLUSIONS: Beclin-1 was highly expressed in GBCA, and positive expression in cancer cells was significantly related with favorable prognosis in GBCA patients. Our results suggest that the expression of Beclin-1 may be an independent predictive marker of favorable prognosis in GBCA.

Expression of multidrug resistance-associated protein 2 in human gallbladder carcinoma.

Gallbladder carcinoma (GBCA) is one of the most aggressive malignancies. It is usually diagnosed at an advanced stage, and prognosis remains poor despite advances in imaging techniques and aggressive surgical treatment. Overexpression of multidrug resistance-associated proteins (MRPs) in tumor cells is a major cause of the intrinsic multidrug resistance phenotype. Despite the documented importance of MRP expression in many carcinomas, the prognostic significance of MRP2 expression in primary GBCA is not known. Immunostaining for MRP2 was performed on tissue samples obtained from 143 patients with GBCA. We examined the association between MRP expression and clinicopathological characteristics and outcome of patients with GBCA. GBCA demonstrated MRP2 immunoreactivity in the apicolateral membranes of epithelial cells. MRP2 expression was positive in 53.1% (76/143) of GBCA samples. Positive MRP2 expression was significantly associated with the presence of local recurrence (P = 0.038), lymphatic invasion (P = 0.038), vascular invasion (P = 0.023), and perineural invasion (P = 0.006). In addition, the median survival time of patients with MRP2-positive GBCA (15 months) was significantly shorter than that of patients with MRP2-negative GBCA (85 months, P = 0.011). We found that the expression of MRP2 in GBCA contributed to aggressive tumor behavior and poor prognosis, suggesting that MRP2 expression can be used as a potential prognostic biomarker of GBCA.