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).


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.


CONCLUSIONS
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.
Bonaccorsi
L
L
Unit of Andrology, Department of Clinical Physiopathology, University of Florence, Florence, Italy. l.bonaccorsi@dfc.unifi.it
Nesi
G
G
Nuti
F
F
Paglierani
M
M
Krausz
C
C
Masieri
L
L
Serni
S
S
Proietti-Pannunzi
L
L
Fang
Y
Y
Jhanwar
S C
SC
Orlando
C
C
Carini
M
M
Forti
G
G
Baldi
E
E
Luzzatto
L
L
D055011:Ablation Techniques; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D050939:Gene Fusion; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000517:prevention & control* / Q000628:therapy*; D012008:Recurrence; D016896:Treatment Outcome
D000726:Androgen Antagonists; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D017430:Prostate-Specific Antigen