Alba Font-Tello1, Núria Juanpere1,2, Silvia de Muga2, Marta Lorenzo1, José A Lorente3,4, Lluis Fumado3,4, Laia Serrano5,4, Sergio Serrano1,4, Josep Lloreta1,2, Silvia Hernández2. 1. Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain. 2. Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain. 3. Department of Urology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain. 4. Autonomous University of Barcelona, Barcelona, Spain. 5. Department of Pathology, Hospital Universitari Germans Tries i Pujol, Barcelona, Spain.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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