Overexpression of Histone Deacetylase 2 Predicts Unfavorable Prognosis in Human Gallbladder Carcinoma

As important regulators of chromatin, histone deacetylases (HDACs) are involved in silencing tumor suppressor genes. HDAC2, a member of HDACs, has been demonstrated to be implicated in the development and progression of various human malignancies; however, its expression and role in human primary gallbladder carcinoma (PGC) are not fully understood. Therefore, we conducted this study to address this problem. The subjects were 136 patients underwent resection for PGC. Immunostainings for HDAC2 were performed on these archival tissues. The correlation of HDAC2 expression with clinicopathological characteristics including survival was analyzed. HDAC2 was positively expressed in the nucleus of tumor cells in 86.0 % (117/136) of PGC but not in the normal epithelium of the gallbladder. Additionally, there was a significant difference in the incidence of positive nodal metastasis between high and low HDAC2 expression groups (P = 0.001). The incidences of advanced clinical stage (P = 0.005) and pathologic T stage (P < 0.001), and higher histologic grade (P < 0.001) were respectively higher in the high HDAC2 expression group than in the low group. Moreover, univariate and multivariate analyses revealed the high HDAC2 expression to be an independent prognostic factor for both overall and disease-free survival of patients with PGC. High HDAC2 expression was correlated with a high incidence of lymph node metastasis and aggressive tumor progression of PGC. It also was an independent prognostic factor for poorer overall and disease-free survival in patients. Therefore, detection of HDAC2 expression may help us screen patients at increased risk of malignant behavior for PGC.