Expression of the Androgen-Regulated Fusion Gene TMPRSS2-ERG Does Not Predict Response to Endocrine Treatment in Hormone-Naïve, Node-Positive Prostate Cancer

Boormans, Joost L.; Hermans, Karin G.; Made, Angelique C. J. Ziel-van der; Leenders, Geert J.H.L. van; Wildhagen, Mark F.; Collette, Laurence; Schröder, Fritz H.; Trapman, Jan; Verhagen, Paul C.M.S.

doi:10.1016/j.eururo.2009.08.013

Cited by 32 publications

(26 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Altogether, these data indicate that 8q gain has prognostic value independently from treatment modality. On the other hand, the TMPRSS2-ERG gene fusion was not associated with disease-specific survival in HT treated patients, which is agreement with previous reports (Boormans et al, 2010;Leinonen et al, 2010) nor with any other treatment subset. Recently, El Gammal et al (2010) found association of 8q gain with BR in patients treated by RP, but multivariate analysis showed no independent predictive effect.…”

Section: Pca Prognosis Of 8q Gain and Tmprss2-ergsupporting

confidence: 93%

Relative 8q gain predicts disease‐specific survival irrespective of the TMPRSS2‐ERG fusion status in diagnostic biopsies of prostate cancer

Barros-Silva

Ribeiro

Rodrigues

et al. 2011

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Screening tools have greatly improved prostate cancer (PCa) detection, but the disease course is heterogeneous, and standard clinicopathological parameters do not fully discriminate aggressive from indolent tumors. To evaluate the prognostic value of the TMPRSS2-ERG fusion gene combined with chromosome arm 8q relative gain in diagnostic biopsies of PCa, we studied a consecutive series of 200 diagnostic needle biopsies from patients with 10-year disease-specific survival data. TMPRSS2-ERG fusion gene status and relative 8q gain were assessed by fluorescent in situ hybridization in whole formalin fixed paraffin-embedded biopsies. The TMPRSS2-ERG fusion gene was detected in 43.5% of PCa and was associated with lower Gleason score (P = 0.045), whereas relative 8q gain was present in 48% of PCa and was associated in high-Gleason score (P < 0.001). ERG rearrangement alone was not associated with clinical outcome, whereas relative 8q gain predicted worse disease-specific survival in PCa patients both with and without the TMPRSS2-ERG fusion gene (P < 0.001), independently of Gleason score, clinical stage, and treatment modality. We conclude that relative 8q gain in diagnostic needle biopsies is a poor prognostic factor independent of the TMPRSS2-ERG fusion gene status and of standard clinicopathological parameters.

show abstract

Section: Pca Prognosis Of 8q Gain and Tmprss2-ergsupporting

confidence: 93%

Relative 8q gain predicts disease‐specific survival irrespective of the TMPRSS2‐ERG fusion status in diagnostic biopsies of prostate cancer

Barros-Silva

Ribeiro

Rodrigues

et al. 2011

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…We studied 71 hormone-naïve prostate cancer lymph node metastases. Although you might expect an important role for TMPRSS2-ERG in the success of endocrine treatment because of the androgen-regulation of TMPSS2 expression, in this group of patients no association between TMPRSS2-ERG expression and time to development of castration resistant disease was detected (Boormans et al 2010). ERG-positive tumors in CRPC patients who were treated with the inhibitor of testosterone synthesis abiraterone acetate were more frequent in patients who responded well to the therapy than in patients who did not show a good response (Attard et al 2009).…”

Section: Ets Fusions As Diagnostic and Prognostic Markers Of Prostatementioning

confidence: 75%

ETS fusion genes in prostate cancer

Tandefelt¹,

Boormans²,

Hermans³

et al. 2014

Endocrine-Related Cancer

Self Cite

View full text Add to dashboard Cite

Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency, other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostatespecific. During the last few years, novel concepts of the process of gene fusion have emerged, and initial experimental results explaining the function of the ETS genes ERG and ETV1 in prostate cancer have been published. In this review, we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate cancer.

show abstract

“…8,[19][20][21][22][23] This variability might be due to differences in study cohorts, clinical end points and methodologies for detecting gene fusion. For example, RT-PCR-detected TMPRSS2-ERG fusion was found in more than 70% of patients surgically treated by radical prostatectomy for prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer

et al. 2012

Self Cite

View full text Add to dashboard Cite

In prostate cancer genomic rearrangements involving genes encoding ETS transcription factors are commonly present, with androgen-regulated transmembrane protease, serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogen homologue (ERG) gene fusion occurring in 40-70%. Studies on the predictive value of ERG rearrangement as detected by in-situ hybridization or polymerase chain reaction have resulted in varying outcomes. The objective of this study was to correlate immunohistochemical ERG protein expression with clinico-pathological parameters at radical prostatectomy specimens, and to determine its predictive value for postoperative disease recurrence and progression in a prostate cancer screening cohort. Since androgen receptor is downregulated by ERG in cell lines, we also compared the expression of respective proteins. We selected 481 participants from the European Randomized Study of Screening for Prostate Cancer treated by radical prostatectomy for prostate adenocarcinoma. A tissue microarray was constructed containing representative cores of all prostate cancer specimens as well as 22 xenografts and seven cell lines. Immunohistochemical expression of ERG and androgen receptor was correlated with prostate-specific antigen (PSA), Gleason sum, pT-stage, surgical margins, biochemical recurrence, local recurrence, overall death and disease-specific death. ERG expression was detected in 284 patients (65%). Expression occurred significantly more frequent in patients with PSA r10 ng/ml (P ¼ 0.024). There was no significant association between ERG and Gleason sum, pT-stage or surgical margin status. PSA (P ¼ 0.011), Gleason sum (P ¼ 0.003), pT-stage (P ¼ 0.001) and surgical margin status (Po0.001) all had independent value for postoperative biochemical recurrence, while positive surgical margin (P ¼ 0.021) was the only independent predictor for local recurrence. ERG protein expression did not have prognostic value for the clinical end points in uni-and multivariate analyses. A positive correlation existed between ERG and androgen receptor expression in single tissue cores (Po0.001). In conclusion, immunohistochemical ERG expression has no predictive value for prostate cancer recurrence or progression after radical prostatectomy. Increasing ERG levels are associated with the upregulation of androgen receptor expression in clinical specimens.

show abstract

Expression of the Androgen-Regulated Fusion Gene TMPRSS2-ERG Does Not Predict Response to Endocrine Treatment in Hormone-Naïve, Node-Positive Prostate Cancer

Cited by 32 publications

References 23 publications

Relative 8q gain predicts disease‐specific survival irrespective of the TMPRSS2‐ERG fusion status in diagnostic biopsies of prostate cancer

Relative 8q gain predicts disease‐specific survival irrespective of the TMPRSS2‐ERG fusion status in diagnostic biopsies of prostate cancer

ETS fusion genes in prostate cancer

ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer

Contact Info

Product

Resources

About