Font-Tello Alba, Juanpere Núria, de Muga Silvia, Lorenzo Marta, Lorente José A, Fumado Lluis, Serrano Laia, Serrano Sergio, Lloreta Josep, Hernández Silvia
Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Prostate. 2015 Aug 1;75(11):1216-26. doi: 10.1002/pros.23004. Epub 2015 May 4.
There 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.
We 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.
Among 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.
Although 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.
关于融合基因TMPRSS2 - ERG在前列腺癌发病机制和进展中的作用，文献中存在争议。TMPRSS2 - ERG融合表达的定量差异在文献中受到的关注非常有限。
我们对一系列前列腺肿瘤中TMPRSS2 - ERG、ERG、PTEN和AR的mRNA水平（n = 83）以及ERG免疫染色（n = 78）进行了定量分析。
在TMPRSS2 - ERG阳性病例（n = 57）中，高融合水平与GS≥8相关（P = 0.025）。ERG mRNA过表达与GS≥8相关（P = 0.047），且与T3 - T4期肿瘤相关（P = 0.032）。在ERG过表达病例（n = 54）中，92.3%的GS≥8肿瘤中发现更高的表达水平（P = 0.02）。ERG免疫染色，无论染色强度如何，也与高分期相关（P = 0.05）。ERG免疫染色与PSA无进展生存期之间存在统计学关联（Log Rank检验，P = 0.048）。PTEN表达降低与TMPRSS2 - 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，PTEN表达降低单独（P = 0.041）以及与TMPRSS2 - ERG（P = 0.04）或ERG过表达（P = 0.04）联合均与GS≥7肿瘤相关。
尽管需要更多研究来进一步阐明它们的作用，但我们的研究结果强调，TMPRSS2 - ERG融合和ERG mRNA的表达水平，而非仅仅其存在与否，与更具侵袭性的表型相关，对预后有影响，并且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有用的预后因素。
