Assessment of Utility of TMPRSS2: ERG Gene Aberrations To Predict Salvage Radiotherapy Prostate Cancer Outcomes
R Mehra, B Han, RJ Lonigro, K Suleman, SA Tomlins, N Palanisamy, DA Hamstra, AM Chinnaiyan, RB Shah. University of Michigan, Ann Arbor, MI
Background: Radiotherapy for biochemical recurrence after radical prostatectomy offers durable salvage rates in about 40-50% patients, and therefore better biomarkers are needed to identify patients unlikely to benefit from this therapy. Gene fusions between androgen regulated TMPRSS2 and ETS transcription factor gene ERG has been proposed as potentially aggressive form of prostate cancer. We examined the relationship between ERG gene fusions and outcomes after salvage radiotherapy for patients with biochemical recurrence after radical prostatectomy.
Design: A tissue microarray representing 61 patients who received salvage radiotherapy for biochemical failure after prostatectomy was analyzed for TMPRSS2 and ERG fusions by fluorescence in situ hybridization assay using 5' and 3' split probes flanking ERG gene. The relationship between ERG rearrangement (translocation and deletion), other risk factors and biochemical failure after salvage radiotherapy with or without associated hormonal treatment were analyzed.
Results: Of 37 analyzable case, 49% demonstrated ERG rearrangement with 45 % rearranged through intronic deletion of 5' ERG. Rearrangement of ERG through 5' deletion is previously associated with androgen independent metastatic PCA and poor outcome in clinically localized prostate cancer. In the present cohort, there was a trend for ERG rearrangement through deletion with greater risk of PSA recurrence after initial response to salvage radiotherapy (P= 0.07).
Conclusions: In this study there is a trend for ERG fusion through deletion and association with increased biochemical failure rates after salvage radiotherapy. This molecular subtype may provide a value in the risk assessment for patients likely to harbor subclinical metastasis for biochemical failure after radical prostatectomy and of need for early systemic therapy.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 129, Monday Morning