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Hernandez S.,University Pompeu Fabra | Font-Tello A.,Hospital Del Mar Parc de Salut Mar IMIM | Juanpere N.,University Pompeu Fabra | De Muga S.,University Pompeu Fabra | And 8 more authors.
Prostate | Year: 2016

BACKGROUND SLC45A3 is the second most common ERG partner in prostate cancer (PrCa). Coexisting TMPRSS2 and SLC45A3 rearrangements are found in a subset of cases, but the meaning is still unknown. METHODS SLC45A3-ERG and TMPRSS2-ERG rearrangements and their association with ERG and PTEN expression and with clinical and pathological features have been analyzed in 80 PrCa (PSMAR-Biobank, Barcelona, Spain). ERG and PTEN mRNA were assessed by qRT-PCR; TMPRSS2-ERG and SLC45A3-ERG by RT-PCR, FISH, and direct sequencing; and ERG expression by IHC. The endpoints were Gleason score (GS), stage, and PSA progression-free survival. RESULTS Single TMPRSS2-ERG was found in 51.6% GS ≤ 7 and 22.2% GS ≥ 8 tumors (P = 0.027). SLC45A3-ERG was found in 25 cases, 20 of them with concurrent TMPRSS2-ERG rearrangement: 11.5% GS = 6, 22.2% GS = 7, and 50% GS ≥ 8 tumors (P = 0.013). Double rearrangements were associated with higher levels of ERG mRNA (P = 0.04). Double rearrangement plus PTEN loss was detected in 0% GS = 6; 14.7% GS = 7, and 29.4% GS ≥ 8 tumors (P = 0.032). Furthermore, this triple change was present in 19.2% stage T3-4 but not in any of stage T2 tumors (P = 0.05). No relationship was found with PSA progression-free survival. CONCLUSIONS Single TMPRSS2-ERG translocation is associated with low grade PrCa. Subsequent development of SLC45A3-ERG results in higher ERG expression. The combination of double rearrangement plus PTEN loss, according to our series, is never found in low grade, low stage tumors. These findings could be potentially useful in therapeutic decision making in PrCa. Tumors with combined TMPRSS2-ERG/SLC45A3-ERG fusions plus PTEN loss should be excluded from watchful waiting and are candidates for intensive therapy. © 2016 Wiley Periodicals, Inc.

De Muga S.,Hospital Del Mar Parc de Salut Mar IMIM | De Muga S.,Autonomous University of Barcelona | Hernandez S.,University Pompeu Fabra | Salido M.,Molecular Cytogenetics Laboratory | And 9 more authors.
Cancer Biomarkers | Year: 2012

The TMPRSS2-ERG fusion has been reported in 42 to 78% of prostate tumors. More than 90% of ERG-overexpressing tumors harbor the fusion. The relationship between the TMPRSS2-ERG fusion and prognosis is controversial. Different studies have suggested an association between CXCR4 and ERG overexpression resulting from the TMPRSS2-ERG rearrangement. The aim of this study was to investigate the relationship between CXCR4 expression, TMPRSS2-ERG fusion and Gleason grade in prostate cancer. TMPRSS2-ERG rearrangement was investigated by FISH (n = 44), ERG protein by IHC (n = 84), and CXCR4 by quantitative RT-PCR (n = 44). TMPRSS2-ERG rearrangement and ERG protein expression were present in almost 50% of the cases, without statistical differences between the different Gleason score groups. There was a very high concordance between FISH and IHC techniques (Kappa Index = 0.954). Seventy percent of Gleason ≥ 8 prostate tumors overexpressed CXCR4 mRNA, and the difference in CXCR4 expression with Gleason < 8 cases was statistically significant (p = 0.009). There was no association between ERG protein and CXCR4 mRNA expression. In conclusion, our results reveal for the first time that CXCR4 overexpression is associated with high Gleason score prostate tumors, but that it is independent of the TMPRSS2-ERG rearrangement. © 2012/2013 - IOS Press and the authors. All rights reserved.

Font-Tello A.,Hospital Del Mar Parc de Salut Mar IMIM | Juanpere N.,Hospital Del Mar Parc de Salut Mar IMIM | Juanpere N.,University Pompeu Fabra | De Muga S.,University Pompeu Fabra | And 12 more authors.
Prostate | Year: 2015

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. © 2015 Wiley Periodicals, Inc.

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