The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: a cohort study and meta-analysis.
BACKGROUND
Whether the genomic rearrangement transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (ERG) has prognostic value in prostate cancer is unclear.


METHODS
Among men with prostate cancer in the prospective Physicians' Health and Health Professionals Follow-Up Studies, we identified rearrangement status by immunohistochemical assessment of ERG protein expression. We used Cox models to examine associations of ERG overexpression with biochemical recurrence and lethal disease (distant metastases or cancer-specific mortality). In a meta-analysis including 47 additional studies, we used random-effects models to estimate associations between rearrangement status and outcomes.


RESULTS
The cohort consisted of 1,180 men treated with radical prostatectomy between 1983 and 2005. During a median follow-up of 12.6 years, 266 men experienced recurrence and 85 men developed lethal disease. We found no significant association between ERG overexpression and biochemical recurrence [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.78-1.26] or lethal disease (HR, 0.93; 95% CI, 0.61-1.43). The meta-analysis of prostatectomy series included 5,074 men followed for biochemical recurrence (1,623 events), and 2,049 men followed for lethal disease (131 events). TMPRSS2:ERG was associated with stage at diagnosis [risk ratio (RR)(≥T3 vs. T2), 1.23; 95% CI, 1.16-1.30) but not with biochemical recurrence (RR, 1.00; 95% CI, 0.86-1.17) or lethal disease (RR, 0.99; 95% CI, 0.47-2.09).


CONCLUSIONS
These results suggest that TMPRSS2:ERG, or ERG overexpression, is associated with tumor stage but does not strongly predict recurrence or mortality among men treated with radical prostatectomy.


CONCLUSIONS
This is the largest prospective cohort study to examine associations of ERG overexpression and lethal prostate cancer among men treated with radical prostatectomy.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. apetters@hsph.harvard.edu
Andreas
A
Pettersson
Rebecca E
RE
Graff
Scott R
SR
Bauer
Michael J
MJ
Pitt
Rosina T
RT
Lis
Edward C
EC
Stack
Neil E
NE
Martin
Lauren
L
Kunz
Kathryn L
KL
Penney
Azra H
AH
Ligon
Catherine
C
Suppan
Richard
R
Flavin
Howard D
HD
Sesso
Jennifer R
JR
Rider
Christopher
C
Sweeney
Meir J
MJ
Stampfer
Michelangelo
M
Fiorentino
Philip W
PW
Kantoff
Martin G
MG
Sanda
Edward L
EL
Giovannucci
Eric L
EL
Ding
Massimo
M
Loda
Lorelei A
LA
Mucci
D000368:Aged; D015331:Cohort Studies; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012697:Serine Endopeptidases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D016896:Treatment Outcome
C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human