[871] Correlation between ERG Immunohistochemical Expression and Radiation Response in Prostate Cancer

Anuradha Gopalan, Ying-Bei Chen, Hikmat Al-Ahmadie, Samson Fine, James Eastham, Satish Tickoo, Victor Reuter. Memorial Sloan-Kettering Cancer Center, New York, NY

Background: TMPRSS2-ERG gene fusions occur in about 50% of prostate cancers with resultant overexpression of a protooncogene, ERG. It is now known that ERG overexpression, concomitantly with other genetic alterations, leads to accelerated prostate carcinogenesis. The prognostic significance of this overexpression, however, is still controversial, and targeting the gene therapeutically has proved difficult. A recent report has suggested that overexpression of the TMPRSS2-ERG fusion product induces DNA damage in PC3 cell lines, which implies increased radiosensitivity. Another recent study has shown that expression of TMPRSS2-ERG fusion in PC3 cells caused persistent unrepaired DNA breaks and thus increased radiosensitivity. Further, they showed that in DU145 cells the response differed based on fusion type: type 3 fusions did not alter radiosensitivity while type 6 fusions increased radioresistance. There is no published data on ERG expression in irradiated human prostate cancer. Our aim was to investigate the utility of the ERG antibody as a biomarker in residual/recurrent prostate cancer after radiation therapy.
Design: ERG IHC (rabbit mAB; clone EPR3864; Epitomics; 1:250 dilution) was performed on a TMA consisting of gradable tumors from 38 patients with prostate cancer who had failed radiation treatment and subsequently undergone salvage radical prostatectomy. The control group was a cohort of 521 patients who underwent radical prostatectomy for clinically localized disease without prior radiation therapy, where we had previously determined TMPRSS2-ERG fusion status by a FISH assay.
Results: Of the 38 cases represented in the TMA, 36 were evaluable. ERG antibody was positive in 17 (47%) and negative in 19 (53%). In the control non-irradiated group, 42% of the population had TMPRSS2-ERG fusion. There was no difference in pathological stage between ERG positive and negative cancers in the post radiation cohort.
Conclusions: 1. The incidence of TMPRSS2-ERG fusion is similar in prostate cancers without prior radiation therapy and cancers which failed radiation therapy, thereby suggesting that ERG negative tumors were not preferentially selected among radiation-resistant tumors in this cohort.
2. ERG positive and negative irradiated prostate cancers had a similar distribution of pathologic stage.
3. Further studies, including interaction of the fusion with other functional cofactors, are necessary to validate the assessment of the fusion as a potential biomarker of treatment response.
Category: Genitourinary (including renal tumors)

Monday, March 19, 2012 1:00 PM

Poster Session II # 163, Monday Afternoon

 

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