Nuclear C-MYC expression level is associated with disease progression and potentially predictive of two year overall survival in prostate cancer.
Nuclear C-MYC expression level is associated with disease progression and potentially predictive of two year overall survival in prostate cancer.
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发表时间：
2015-02
影响因子：
1.4
通讯作者：
W. Zeng;Han-ying Sun;Fankai Meng;Zeming Liu;J. Xiong;Sheng Zhou;Fan Li;Jia Hu;Zhiquan Hu;Zheng Liu
中科院分区：
文献类型：
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作者：
W. Zeng;Han-ying Sun;Fankai Meng;Zeming Liu;J. Xiong;Sheng Zhou;Fan Li;Jia Hu;Zhiquan Hu;Zheng Liu
核C-MYC蛋白表达上调是前列腺癌（PCa）的早期事件，但其临床病理和预后意义仍存在争议。我们确定了PCa细胞核C-MYC蛋白表达与临床病理参数、预后、ETS相关基因（ERG）表达和TMPRSS 2-ERG状态的关系。方法采用免疫组织化学方法检测50例PCa患者和31例根治性PCa手术标本中C-MYC和ERG的表达，采用三色荧光探针原位杂交法检测TMPRSS 2-ERG的表达。结果27.5%、32.5%和40.0%的乳腺癌细胞核C-MYC免疫染色呈阴性、阳性和强阳性。C-MYC免疫染色与临床T分期（P < 0.001）、确诊时远处转移（P < 0.001）和TMPRSS 2-ERG状态（P = 0.001）显著相关，但与ERG免疫染色无关（P = 0.818）。在Kaplan-Meier分析中，发现C-MYC阳性病例的2年OS比C-MYC阴性病例差（P = 0.027）。然而，在单变量考克斯分析中，只有TMPRSS 2-ERG状态（风险比[HR] 0.189，95% CI 0.057-0.629; P = 0.007）和远处转移（HR 3.545，95% CI 1.056-11.894; P = 0.040）与2年OS显著相关。调整这两个因素后，TMPRSS 2-ERG状态仍影响2年OS（HR 0.196，95% CI 0.049-0.778; P = 0.020）。结论：核C-MYC过表达可能与PCa的疾病进展相关，并可能预测PCa的2年OS。这是第一项证明PCa细胞核C-MYC免疫染色和TMPRSS 2-ERG状态之间相关性的研究。
PURPOSE Upregulation of nuclear C-MYC protein has been reported to be an early event in prostate cancer (PCa); however, its clinicopathological and prognostic significance remain controversial. We determined the association of nuclear C-MYC protein expression with clinicopathological parameters, prognosis, ETS-related gene (ERG) expression, and TMPRSS2-ERG status in PCa. METHODS Nuclear C-MYC and ERG expression by immunohistochemistry and TMPRSS2-ERG status by triple-color probe fluorescence in situ hybridization assay were determined in 50 hormone-naïve PCa patients and 31 radical prostatectomy specimens. RESULTS Nuclear C-MYC immunostaining was negative, positive, and strong positive in 27.5%, 32.5%, and 40.0% of cases, respectively. C-MYC immunostaining was significantly associated with clinical T stage (P < 0.001), distant metastasis at the time of diagnosis (P < 0.001) and TMPRSS2-ERG status (P = 0.001) but not with ERG immunostaining (P = 0.818). In the Kaplan-Meier analysis, C-MYC positive cases were found to have worse 2-year OS compared with C-MYC negative cases (P = 0.027). However, in the univariate Cox analysis, only TMPRSS2-ERG status (hazard ratio [HR] 0.189, 95% CI 0.057-0.629; P = 0.007) and distant metastasis (HR 3.545, 95% CI 1.056-11.894; P = 0.040) were significantly associated with 2-year OS. After adjusting for these two factors, TMPRSS2-ERG status still impacted 2-year OS (HR 0.196, 95% CI 0.049-0.778; P = 0.020). CONCLUSIONS Nuclear C-MYC overexpression may be associated with disease progression and potentially predictive of 2-year OS in PCa. This is the first study to demonstrate an association between nuclear C-MYC immunostaining and TMPRSS2-ERG status in PCa.