Nuclear localization of annexin A1 is a prognostic factor in oral squamous cell carcinoma

Abstract

To investigate whether annexin A1 (ANXA1) expression is a marker in predicting the prognosis of oral cancer patients. We immunohistochemically examined the expression of ANXA1 in 66 cases of oral epithelial dysplasia (OED) and 115 cases of oral squamous cell carcinoma (OSCC). The results were correlated with the clinicopathological parameters of tumors and overall patient survival. In normal oral mucosa, ANXA1 staining was predominantly located on the cell membrane. In OED and OSCC specimens, membranous staining decreased, whereas nuclear staining increased. Positive nuclear staining was observed in 9 of 66 (13.64%) OED cases and 63 of 115 (54.8%) OSCCs. Kaplan-Meier curves showed that OSCC patients with ANXA1 nuclear staining had significantly shorter overall lengths of survival (P = 0.00036 by the log-rank test). Multivariate analysis showed that ANXA1 nuclear staining is a significant predictor of poor overall survival. And oral cancer SAS cells treated with hepatocyte growth factor (HGF) can induce ANXA1 protein translocation from cytoplasm to nucleus. Cells pretreated with LY294002 (PI3K inhibitor) almost completely inhibited (88.3% inhibition) HGF-mediated ANXA1 nuclear translocation. The nuclear localization of ANXA1 protein is a frequent event and could be used as a prognostic factor in OSCC.