EZH2 protein expression associates with the early pathogenesis, tumor progression, and prognosis of non-small cell lung carcinoma.
EZH2 protein expression associates with the early pathogenesis, tumor progression, and prognosis of non-small cell lung carcinoma.
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DOI：
10.1158/1078-0432.ccr-12-3946
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发表时间：
2013-12-01
期刊：
影响因子：
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通讯作者：
Wistuba II
中科院分区：
文献类型：
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作者：
Behrens C;Solis LM;Lin H;Yuan P;Tang X;Kadara H;Riquelme E;Galindo H;Moran CA;Kalhor N;Swisher SG;Simon GR;Stewart DJ;Lee JJ;Wistuba II
ZAST同源增强子2(EZH2)通过表观遗传沉默肿瘤抑制基因促进肿瘤的发生。我们用免疫组织化学方法研究了EZH2在一大系列非小细胞肺癌(NSCLC)中的表达与肿瘤特征和患者预后的关系。应用免疫组织化学方法检测265例正常及癌前病变、541例原发非小细胞肺癌(221例鳞癌和320例腺癌)及36例有脑转移的非小细胞肺癌组织中EZH2的表达。另一组独立的91例腺癌也进行了检查。EZH2的表达与临床病理信息、EGFR/KRAS突变状态相关。EZH2在鳞癌中的表达显著高于腺癌(P<；0.0001)，在脑转移癌中的表达明显高于匹配的原发肿瘤(P=0.0013)。随着病变程度的加重，EZH2的表达显著升高(P<；0.0001)。在腺癌中，EZH2的高表达与年龄、吸烟和高TNM分期显著相关(P=0.02P<；0.0001)。腺癌中EZH2的高表达与无复发生存期(RFS；P=0.025；HR1.54)和总生存期(OS；P=0.0002；HR1.96)相关。此外，在91例独立的肺腺癌中，EZH2水平低和家族特异性转录因子TTF1高表达的肺腺癌，其RFS(P=0.009；HR0.51)和OS(P=0.0011；HR0.45)显著改善。在肺组织中，EZH2的表达参与了鳞癌的早期发病过程，并与腺癌的侵袭性肿瘤行为相关。当EZH2和TTF-1的表达一起考虑时，它们可以作为手术切除的肺腺癌患者的预后标志物。
Enhancer of zeste homolog 2 (EZH2) promotes carcinogenesis by epigenetically silencing tumor suppressor genes. We studied EZH2 expression by immunohistochemistry in a large series of non-small cell lung carcinomas (NSCLC) in association with tumor characteristics and patient outcomes. EZH2 immunohistochemistry expression was analyzed in 265 normal and premalignant bronchial epithelia, 541 primary NSCLCs [221 squamous cell carcinomas (SCCs) and 320 adenocarcinomas] and 36 NSCLCs with paired brain metastases. An independent set of 91 adenocarcinomas was also examined. EZH2 expression was statistically correlated with clinico-pathological information, and EGFR/KRAS mutation status. EZH2 expression was significantly (P<0.0001) higher in SCCs compared to adenocarcinomas and in brain metastasis relative to matched primary tumors (P=0.0013). EZH2 expression was significantly (P<0.0001) elevated in bronchial preneoplastic lesions with increasing severity. In adenocarcinomas, higher EZH2 expression significantly correlated with younger age, cigarette smoking and higher TNM stage (P=0.02 to P<0.0001). Higher EZH2 expression in adenocarcinoma was associated with worse recurrence-free survival (RFS; P=0.025; HR 1.54) and overall survival (OS; P=0.0002; HR 1.96). Furthermore, lung adenocarcinomas with low EZH2 levels and high expression of the lineage-specific transcription factor, TTF-1, exhibited significantly improved RFS (P=0.009; HR 0.51) and OS (P=0.0011; HR 0.45) which was confirmed in the independent set of 91 adenocarcinomas. In lung, EZH2 expression is involved in early pathogenesis of SCC and correlates with a more aggressive tumor behavior of adenocarcinoma. When EZH2 and TTF-1 expressions are considered together, they serve as a prognostic marker in patients with surgically resected lung adenocarcinomas.