Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China.
Pathol Oncol Res. 2013 Jul;19(3):397-403. doi: 10.1007/s12253-012-9592-y. Epub 2012 Dec 16.
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.
作为染色质的重要调节因子，组蛋白去乙酰化酶（HDACs）参与肿瘤抑制基因的沉默。HDAC2 是 HDACs 的成员之一，已被证明与多种人类恶性肿瘤的发生和发展有关；然而，其在人原发性胆囊癌（PGC）中的表达和作用尚未完全了解。因此，我们进行了这项研究来解决这个问题。研究对象为 136 例接受胆囊癌切除术的患者。对这些存档组织进行了 HDAC2 免疫染色。分析了 HDAC2 表达与包括生存在内的临床病理特征的相关性。在 86.0%（117/136）的 PGC 肿瘤细胞核中 HDAC2 呈阳性表达，但在胆囊正常上皮中不表达。此外，高表达和低表达 HDAC2 组之间阳性淋巴结转移的发生率存在显著差异（P=0.001）。高表达 HDAC2 组的临床分期较晚（P=0.005）、病理 T 分期较高（P<0.001）和组织学分级较高（P<0.001）的发生率均高于低表达组。此外，单因素和多因素分析显示，高 HDAC2 表达是 PGC 患者总生存和无病生存的独立预后因素。高 HDAC2 表达与 PGC 淋巴结转移发生率高和肿瘤侵袭性进展相关。它也是影响 PGC 患者总生存和无病生存的独立预后因素。因此，检测 HDAC2 表达可能有助于我们筛选出恶性行为风险较高的 PGC 患者。
