Expression And Significance Of HMGB1 Protein In Endometrial Adenocarcinoma

Backgroud:Endometrial carcinoma is a primary epithelial malignant tumor and one of the most common female genital cancers. Its incidence is increasing year by year.80% of endometrial carcinomas are endometrial adenocarcinoma that is intently related with estrogen. High mobility group box 1 (HMGB1) protein is a highly conserved non-histone, nuclear DNA-binding protein. HMGB1 is demonstrated to serve as a cytokine that mediates late systemic inflammation via its extracellular release from activated macrophages/monocytes and cells undergoing apoptosis or necrosis. Many previous studies have observed the over-expression of HMGB1 with its receptor, receptor for advanced glycation end products (RAGE), in different malignant tumors. Some investors consider that the over-expressed HMGB1 induces the tumor genesis, invasion and metastasis by regulating genes expression. The interaction of HMGB1 with other transcription factors has also been found, including the steroid hormone receptors, especially in estrogen stimulated breast cancer cells. The role of HMGB1 in endometrial carcinoma is unknown.Object:To investigate the expression of HMGB1 (high mobility group boxl, HMGB1) in human endometrial adenocarcinoma and ECC-1,HEC-1-a,KLE cell, and to explore its relation to the differentiation grade, invasion, metastasis and operative-pathological staging of human endometrial adenocarcinoma. To investigate the correlation of serum HMGB1 levels and clinical and pathological characters of carcinoma of endometrium, and to assess the viability of HMGB1 as a biomarker for the diagnosis for carcinoma of endometrium.Methods:Immunohistochemical staining was used to detect the expression of HMGB1 in 45 atypical hyperplasia endometria,120 endometrial adenocarcinomas and 20 normal endometria, and western blot was applied to analysis the expression level of HMGB1. We also detected the expression of HMGB1 in high, moderate and low grade endometrial adenocarcinoma cell (ECC-1, HEC-1-a, KLE) by immunocytochemistry and western blot. Concurrently the subject serum levels of HMGB1 of 40 endometrial adenocarcinomas patients and 40 normal women were detected by an enzyme-linked immunosorbent assay (ELISA) method.Results:The positive expression rate of HMGB1 were 80.00%(96/120), 66.67%(30/45) in endometrial adenocarcinoma and atypical hyperplasia endometrium, respectively, which were significantly higher than that in normal endometria 5.00%(1/20). The positive expression rate of HMGB1 is significantly correlated with the invasion, metastasis and operative-pathological staging of human endometrial adenocarcinoma(P<0.05), while it showed no significant correlation with the grade(P>0.05). The expression of HMGB1 in ECC-1, HEC-1-a and KLE cells were both positive with immunocytochemistry and western blot, but the difference of expression level is not significant. The mean serum levels of HMGB1 were 3.34±1.58 ng/ml in the normal group,6.42±2.82ng/ml in stageⅠ,9.85±5.25ng/ml in stageⅡ, 14.26±7.86ng/ml in stageⅢ/Ⅳ. The serum levels of HMGB1 were notably different among the each group (ANOVA, P<0.01). The levels were tended to increase according to the evolution of endometrial adenocarcinoma.Conclusion:The over expression of HMGB1 in endometrial adenocarcinoma may be played an important role in carcinogenesis and development in endometrial adenocarcinoma. We suggest that HMGB1 protein could be used as a useful marker for diagnosis of human endometrial adenocarcinoma.