Expression of Astrocyte Elevated Gene-1 A Novel Marker of the Pathogenesis, Progression, and Poor Prognosis for Endometrial Cancer

Objective: To assess the expression of astrocyte elevated gene-1 (AEG-1) in different endometrial specimens and to investigate its relationship with clinicopathological features and its impact on patient outcome. Materials and Methods: By Western blot analysis, we investigated AEG-1 expression in paired endometrial tissues and adjacent nontumor tissues of the same patients (n = 4). Immunohistochemistry analysis was used to determine the expression levels of AEG-1 protein in 35 normal endometrium, 40 atypical endometrial hyperplasia, and 174 endometrial cancers. The correlation between AEG-1 expression and various clinicopathological characteristics of endometrial cancer patients was analyzed. Results: Western blot analysis showed that AEG-1 expression levels were up-regulated in all 4 human primary endometrial cancer tissues compared with their matched adjacent noncancerous tissues. The frequent and strong expression of AEG-1 was gradually elevated in normal endometrial tissue, atypical hyperplasia, and endometrial cancers (P < 0.001). Although AEG-1 staining mainly emerged in the cytoplasm, a nuclear distribution was observed in both invasive and advanced endometrial cancer cells. The Ki67 (a proliferation marker) was frequently expressed in the high AEG-1-expressed area, whereas areas with low AEG-1 levels showed weak Ki67 expression. Astrocyte elevated gene-1 overexpression was positively correlated with the International Federation of Gynecology and Obstetrics stage, depth of myometrial invasion, lymph node metastasis, lymph vascular space invasion, and recurrence but not with age or histological type. Patients with high AEG-1 expression had significantly poor overall survival and disease-free survival compared with patients with AEG-1 low expression (both P G 0.001). Multivariate Cox proportional hazards regression demonstrated that high AEG-1 expression was an independent prognostic factor for both the overall survival and disease-free survival of patients with endometrial cancer (P = 0.002 and P = 0.004, respectively). Conclusion: Astrocyte elevated gene-1 overexpression may be associated with carcinogenesis and tumor progression in endometrial cancer. Moreover, it may be a new prognostic marker or a target for improving the treatment efficiency of patients with endometrial cancer.