State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
Int J Cancer. 2010 Jul 1;127(1):138-47. doi: 10.1002/ijc.25031.
The enhancer of zeste homolog 2 (EZH2), a known repressor of gene transcription, has been reported to be associated with biological malignancy in several cancers. The potential oncogenic role of EZH2 and its clinical/prognostic significance, however, in esophageal squamous cell carcinoma (ESCC) are unclear. In this study, the methods of immunohistochemistry and fluorescence in-situ hybridization were used to examine protein expression and amplification of EZH2 in 98 pretreatment biopsy specimens of ESCC who received definitive chemoradiotherapy (CRT). High expression of EZH2 and amplification of EZH2 was found in 54.1% and 12.0% of ESCCs, respectively. High EZH2 expression was significantly correlated with increased cell proliferation (p = 0.009), high histopathological grade (p = 0.002), regional (p = 0.025) and distant lymph node metastasis (p < 0.001) and lack of clinical complete response to CRT (p = 0.028). Univariate analysis revealed that high expression of EZH2 was associated with poor metastasis-free survival (MFS) (p = 0.003), poor progression-free survival (PFS) (p = 0.001) and poor disease-specific survival (DSS) (p < 0.001). In multivariate analysis, high expression of EZH2, together with lack of clinical complete response, were evaluated as significant independent prognostic factors of MFS, PFS and DSS for patients with ESCC. These findings suggest that high expression of EZH2 correlates with tumor aggressiveness and adverse patient outcome in ESCC treated with definitive CRT. Evaluation of EZH2 expressions might be useful for predicting tumor response to CRT and prognosis for patients with ESCC.
增强子结合锌指蛋白 2（EZH2）是一种已知的基因转录抑制剂，它已被报道与几种癌症的生物学恶性有关。然而，EZH2 的潜在致癌作用及其在食管鳞状细胞癌（ESCC）中的临床/预后意义尚不清楚。在这项研究中，我们使用免疫组织化学和荧光原位杂交方法检测了 98 例接受根治性放化疗（CRT）的 ESCC 患者的 EZH2 蛋白表达和扩增情况。在 ESCC 中，EZH2 的高表达和扩增分别占 54.1%和 12.0%。EZH2 的高表达与细胞增殖增加（p=0.009）、高组织病理学分级（p=0.002）、局部（p=0.025）和远处淋巴结转移（p<0.001）以及 CRT 临床完全缓解缺失显著相关（p=0.028）。单因素分析显示，EZH2 的高表达与无转移生存（MFS）（p=0.003）、无进展生存（PFS）（p=0.001）和疾病特异性生存（DSS）（p<0.001）差相关。多因素分析显示，EZH2 的高表达以及缺乏临床完全缓解是 ESCC 患者 MFS、PFS 和 DSS 的独立预后因素。这些发现表明，EZH2 的高表达与 ESCC 患者接受根治性 CRT 治疗后的肿瘤侵袭性和不良预后相关。EZH2 表达的评估可能有助于预测 CRT 治疗的肿瘤反应和 ESCC 患者的预后。
