Association of ERG and TMPRSS2-ERG with grade, stage, and prognosis of prostate cancer is dependent on their expression levels
Association of ERG and TMPRSS2-ERG with grade, stage, and prognosis of prostate cancer is dependent on their expression levels
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DOI：
10.1002/pros.23004
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发表时间：
2015-08-01
期刊：
影响因子：
2.8
通讯作者：
Hernandez, Silvia
中科院分区：
文献类型：
--
作者：
Font-Tello, Alba;Juanpere, Nuria;Hernandez, Silvia
背景关于融合TMPRSS 2-ERG在前列腺癌发病机制和进展中的作用，文献中存在争议。方法对83例前列腺肿瘤组织中TMPRSS 2-ERG、ERG、PTEN、AR的mRNA水平及78例ERG免疫组化染色进行了定量分析，结果发现在57例TMPRSS 2-ERG病例中，高融合表达与GS8相关（P=0.025）。ERG mRNA过表达与GS 8（P=0.047）和T3-T4期肿瘤（P=0.032）相关。在ERG高表达的54例肿瘤中，92.3%的GS8肿瘤表达ERG（P=0.02）。ERG免疫染色，无论染色强度，也与高阶段（P=0.05）。ERG免疫染色与PSA无进展生存期之间存在统计学相关性（对数秩检验，P=0.048）。PTEN表达降低与TMPRSS 2-ERG（P=0.01）、ERG mRNA过表达（P=0.003）和ERG免疫染色（P=0.007）相关。此外，单独的PTEN表达降低，（P=0.041），并结合TMPRSS 2-ERG（P=0.04）或ERG过表达（P=0.04）与GS 7肿瘤相关。结论TMPRSS 2-ERG融合蛋白和ERG mRNA的表达水平，而不仅仅是它们的存在，与更具侵袭性的表型相关，对预后有影响，可能是前列腺癌进展的分子标志物。此外，ERG免疫组化也可能是一个潜在的有用的预后因素。前列腺75：1216-1226，2015。(c)2015 Wiley Periodicals，Inc.
BACKGROUNDThere is controversy in the literature on the role of the fusion TMPRSS2-ERG in the pathogenesis and progression of prostate cancer. The quantitative differences in TMPRSS2-ERG fusion expression have received very limited attention in the literature.METHODSWe have quantitatively analyzed the mRNA levels of TMPRSS2-ERG, ERG, PTEN, and AR (n=83), as well as ERG immunostaining (n=78) in a series of prostate tumors.RESULTSAmong the TMPRSS2-ERG cases (n=57), high fusion levels were associated with GS 8 (P=0.025). ERG mRNA overexpression was associated with GS 8 (P=0.047), and with stage T3-T4 tumors (P=0.032). Among the ERG overexpressing cases (n=54), higher expression levels were found in 92.3% of GS 8 tumors (P=0.02). ERG immunostaining, regardless of staining intensity, was also associated with high stage (P=0.05). There was a statistical association between ERG immunostaining and PSA progression-free survival (Log Rank test, P=0.048). Decreased PTEN expression was associated with TMPRSS2-ERG (P=0.01), ERG mRNA overexpression (P=0.003) and ERG immunostaining (P=0.007). Furthermore, decreased PTEN expression, alone (P=0.041) and also combined with TMPRSS2-ERG (P=0.04) or with ERG overexpression (P=0.04) was associated with GS 7 tumors.CONCLUSIONSAlthough more studies are needed to further clarify their role, our findings emphasize that the expression levels of the TMPRSS2-ERG fusion and ERG mRNA, rather than their mere presence, are related to a more aggressive phenotype, have an effect on prognosis and could be molecular markers of progression for prostate cancer. Furthermore, ERG immunohistochemistry could be also a potentially useful prognostic factor. Prostate 75: 1216-1226, 2015. (c) 2015 Wiley Periodicals, Inc.