Persistence of expression of the TMPRSS2:ERG fusion gene after pre-surgery androgen ablation may be associated with early prostate specific antigen relapse of prostate cancer: preliminary results

J Endocrinol Invest. 2009 Jul;32(7):590-6. doi: 10.1007/BF03346514. Epub 2009 May 5.

Abstract

Background: The recently identified TMPRSS2: ERG fusion gene is a candidate oncogene for prostate cancer (PCa).

Subjects and methods: We have tested for the presence of this gene in tumor samples from 84 patients who had radical prostatectomy in 1998-2000. Sixty patients (group A) had surgery only; 24 patients (group B) received androgen ablation therapy for 3 months before surgery. The occurrence of the rearrangement was evaluated by RT-PCR and by fluorescent in situ hybridization analysis.

Results: A TMPRSS2:ERG fusion gene was present and expressed, as demonstrated by RT-PCR, in 84% of patients in group A and in 54% of patients in group B (p=0.01). The presence of TMPRSS2:ERG transcripts and the levels of ERG RNA, measured by quantitative Real Time-PCR, did not correlate significantly with clinical and pathologic characteristics of the tumors. In patients of group A, but not in those of group B, ERG expression showed a negative correlation with the Gleason score (p=0.0001). Histochemical analysis showed that ERG expression is limited to tumor cells, and in group A patients (but not in group B patients) it is limited to those glands that express TMPRSS2:ERG.

Conclusion: The lower proportion of patients expressing TMPRSS2: ERG in group B suggests that androgen ablation inhibits the expression of TMPRSS2:ERG. Moreover, in group B, but not in group A, patients with expression of the fusion gene had earlier prostate specific antigen recurrence (p=0.007). Although preliminary, the data indicate that tumors in which pre-surgery androgen ablation fails to suppress expression of the fusion gene have a higher risk of recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ablation Techniques
  • Aged
  • Androgen Antagonists / therapeutic use*
  • Animals
  • Gene Fusion
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Prostate-Specific Antigen / blood*
  • Prostatectomy
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / prevention & control*
  • Prostatic Neoplasms / therapy*
  • Recurrence
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Oncogene Proteins, Fusion
  • TMPRSS2-ERG fusion protein, human
  • Prostate-Specific Antigen