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

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. (J. Endocrinol. Invest. 32: 590-596, 2009) (C) 2009, Editrice Kurtis