ERG Rearrangement Status Is Associated with Castration Resistant Prostate Cancer.
Maria A Svensson, Sven Perner, Juan-Miguel Mosquera, Katja Fall, Lorelei A Mucci, Swen-Olof Andersson, Ove Andren, Jan-Erik Johansson, Mark A Rubin, Jennifer R Stark. Orebro University Hospital, Orebro, Sweden; Bonn University Hospital, Germany; Weill Cornell Medical College, New York, NY; Karolinska Institutet, Stockholm, Sweden; Harvard School of Public Health, Boston, MA; Brigham & Women's Hospital, Boston, MA
Background: Since the discovery of the TMPRSS2-ERG gene fusion in prostate cancer (PCa) studies have investigated associations between the fusion and clinical outcome of PCa with discrepant results. Most studies show that having the fusion is a sign of a more aggressive disease, but some report that the fusion is associated with more favorable prognostic markers. Few studies have examined the association between fusion-positive cancer and castration resistant disease, despite strong biologic rationale given that TMPRSS2 is androgen regulated. We aimed to investigate if there is an association between fusion status and time to castration resistance.
Design: We utilized 154 patients who were hormonally treated and had data on fusion status available from the Swedish Watchful Waiting cohort that includes PCa cases diagnosed with T1a or T1b cancer with TURP between 1977-99. Castration resistant disease was classified as two consecutive rises in PSA >3ng/ml after hormonal therapy. Fusion status was assessed by FISH using an ERG break-apart assay.
Results: We found an overall ERG rearrangement frequency of 25% (59% rearranged through insertion and 41% through deletion). During a median of 5.5 years, 100 men on hormonal therapy became castration resistant. ERG rearrangement was more common among men who developed castration resistant disease (30.4% vs. 15.4%; p=0.04). Having the rearrangement led to a 75% increase in risk of becoming castration resistant (95% CI: 1.14-2.70). Adjusting for Gleason score, age at diagnosis, calendar year at diagnosis and T-stage, men with fusion-positive tumors were 52% more likely to become castration resistant (95% CI: 0.97-2.38). The attenuation was mainly due to adjustment for Gleason score. Stratifiying according to the two rearrangement mechanisms, we found the increase in risk was limited to those with rearrangement through insertion.
Conclusions: Hormonally treated PCa patients having an ERG rearrangement have a significantly increased risk of becoming castration resistant compared to patients without the rearrangement. The results from our study indicate that the ERG rearrangement is a sign of a more aggressive disease and could potentially be used to identify patients less likely to respond to hormone treatment.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 2:00 PM
Platform Session: Section A, Tuesday Afternoon