Expression of BNIP3 and its correlations to hypoxia-induced autophagy and clinicopathological features in salivary adenoid cystic carcinoma

BACKGROUND: The expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein3 (BNIP3) has been explored in many human malignancies, but not in adenoid cystic carcinoma (ACC). OBJECTIVE: This study investigated the clinical significance of expression of BNIP3 in ACC tissues and cells and elucidated its correlations to hypoxia-induced autophagy. METHODS:Immunohistochemical and immunofluorescence staining were used toexplore BNIP3,HIF-1αand LC3 expression. RESULTS: BNIP3 was positively expressed in 41 cases (63.1%), and was significantly correlated with histological grade (P = 0.001). HIF-1α was positively expressed in 52 cases (80.0%) and was significantly correlated with TNM stage (P = 0.023) and histological grade (P = 0.024). LC3 was positively expressed in 37 cases (56.9%) and was significantly correlated with TNM stage (P = 0.019). The expression of BNIP3 was correlated with HIF-1α expression (P = 0.011). The overall survival in the negative BNIP3 expression group tended to be better than in the positive BNIP3 expression (P = 0.011). In vitro experiment, BNIP3 immunofluorescence staining was detected in cells treated with CoCl2 (for hypoxic condition). CONCLUSIONS: The data indicated that BNIP3 plays a vital role in the tumorigenesis of adenoid cystic carcinoma and could be a new target for gene therapy of adenoid cystic carcinoma.