High expression of EZH2 is associated with tumor aggressiveness and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy
High expression of EZH2 is associated with tumor aggressiveness and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy
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DOI：
10.1002/ijc.25031
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发表时间：
2010-07-01
影响因子：
6.4
通讯作者：
Xie, Dan
中科院分区：
文献类型：
--
作者：
He, Li-Ru;Liu, Meng-Zhong;Xie, Dan
Zeste同源物2增强子（EZH 2）是一种已知的基因转录抑制物，已报道与几种癌症中的生物恶性肿瘤相关。然而，EZH 2在食管鳞状细胞癌（ESCC）中的潜在致癌作用及其临床/预后意义尚不清楚。本研究应用免疫组织化学和荧光原位杂交方法检测了98例接受确定性放化疗（CRT）的ESCC患者术前活检标本中EZH 2的蛋白表达和扩增情况。EZH 2高表达和扩增率分别为54.1%和12.0%。EZH 2高表达与细胞增殖增加（p = 0.009）、高组织病理学分级（p = 0.002）、区域（p = 0.025）和远处淋巴结转移（p < 0.001）以及缺乏对CRT的临床完全响应（p = 0.028）显著相关。单变量分析显示，EZH 2的高表达与差的无转移生存期（MFS）（p = 0.003）、差的无进展生存期（PFS）（p = 0.001）和差的疾病特异性生存期（DSS）（p < 0.001）相关。多因素分析显示，EZH 2高表达和临床完全缓解的缺乏是影响ESCC患者MFS、PFS和DSS的独立预后因素。这些发现表明EZH 2的高表达与用确定性CRT治疗的ESCC中的肿瘤侵袭性和不良患者结果相关。EZH 2表达水平的检测可能有助于预测食管鳞癌患者对CRT的反应和预后。
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.