CONCLUSIONS: In men on active surveillance, %[-2]proPSA and phi were associated with prostate cancer reclassification during follow-up. Additional study is warranted to identify thresholds for clinical use and to examine these markers as part of a multi-marker panel for monitoring patients on active surveillance. Concordance indices for disease reclassification on active surveillance biopsy using baseline and longitudinal data. Age, date of diagnosis, tPSA Baseline Data Concordance Index Longitudinal Data Concordance Index Age, date of diagnosis, tPSA 0.59 0.69 Age, date of diagnosis, %fPSA 0.67 0.70 Age, date of diagnosis, % [-2]proPSA 0.63 0.70 Age, date of diagnosis, [-2]proPSA/%fPSA 0.65 0.73 Age, date of diagnosis, phi 0.67 0.74 Source of Funding: Funding for this project was provided by The Johns Hopkins University Prostate Cancer SPORE (Grant number: P50CA58236), Early Detection Research Network (EDRN) NCI/NIH (Grant number CA086323)-06 and CA115102-04), Prostate Cancer Foundation, Patana 2324 GENETIC RISK ALLELES CAN PREDICT ACTIVE SURVEILLANCE FAILURES Brian T. Helfand, Barry B. McGuire, Chicago, IL; Qiaoyan Hu*, Chicago, Please choose an option below; Daniel C. O’Brien, Cheng Li, Shilajit Kundu, William J. Catalona, Chicago, IL INTRODUCTION AND OBJECTIVES: There is debate as to which prostate cancer (CaP) patients require immediate definitive therapy and which may be safely monitored by active surveillance (AS). Because there are no known biomarkers that can predict aggressive disease, 60% of men may ultimately fail AS protocols. Recent ge- nome-wide association studies have identified genetic alleles that are associated with CaP susceptibility, and perhaps aggressive pathology. However, their utility in predicting AS failures is unknown. METHODS: From March 2003-September 2009, 1376 Caucasian men underwent radical prostatectomy and were genotyped for 17 different risk alleles located on chromosomes 2p15, 3q21m, 5p15, 8q24, 11q13, 17q12, 17q24, 19q13 and Xp11. Candidates for AS were defined by a modified Epstein criteria (JAMA. 1994. 271: 368): clinical stage T1c, PSA10ng/ml, Gleason grade 6, tumor involving 3 cores and no more than 50% of any single core. Failures and successes of AS were defined by the presence or absence of pathologic Gleason grade 7 and/or pathologic stage T3. Comparisons were made between the frequency of risk alleles in failures and successes. RESULTS: 181 (13.2%) men initially met criteria for AS. Of this population, there were 33 (18.2%) failures and 148 (81.8%) suc- cesses. 7 of the 17 CaP risk alleles were over-represented in failures compared to successes. Specifically, there was a significantly higher frequency of the 8q24 risk alleles SNP rs1447295 and SNP rs16902094 in failures compared to successes (Table 1). CONCLUSIONS: Prior studies have suggested that risk loci on 8q24 confer disease aggressiveness (e.g. Eur J Hum Genet. 2008.16: 496). This study suggests that these 8q24 alleles may have utility in selecting appropriate candidates for AS. Future prospective studies are required to further establish the true utility of the CaP risk alleles. Allele Frequencies for Active Surveillance Failures vs. Successes CaP Risk Allele Chromosome Allele Freuency ‘AS Failures‘ Allele Frequency ‘AS Successes‘ p value rs1447295 8q24 30.8% 14.8% 0.04 rs16902094 8q24 29.4% 13.8% 0.02 Source of Funding: Supported in part by the Urological Research Foundation, Prostate SPORE grant (P50 CA90386- 05S2) and the Robert H. Lurie Comprehensive Cancer Center Grant (P30 CA60553) 2325 AUTOANTIBODY SIGNATURES AS BIOMARKERS TO DISTINGUISH PROSTATE CANCER FROM BENIGN PROSTATIC HYPERPLASIA USING A NATIVE ANTIGEN CAPTURE MICROARRAY PLATFORM Dennis O’Rourke*, Daniel DiJohnson, Michael O’Leary, Jerome Richie, Brian Liu, Boston, MA INTRODUCTION AND OBJECTIVES: Serum prostate specific antigen (PSA) levels lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We now report the identification of 5 autoantibody signatures to specific cancer targets which may be capable of ruling out a diag- nosis of cancer for patients with non-malignant prostatic disease, such as BPH, in patients with elevated serum PSA. METHODS: To discover new biomarkers which may distinguish between prostate cancer and BPH, a native antigen capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nano-particle slides to capture native antigens from prostate cancer cells. Using the immobilized antigens as baits, auto- antibodies from prostate cancer patients and patients with BPH can be isolated and probed. From preliminary experiments using an initial set of over 500 cancer related antigens, a customized array containing 27 unique antigens was further tested. Prostate cancer patient (n=41) and BPH patient serum samples with a mean follow-up of 6.8 years without the diagnosis of cancer (n=39) were obtained. 100ug of IgGs were purified and dye labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. For each spot, a signal-to-noise ratio (SNR) was measured to eliminate background interference. Through comparative analysis of the prostate cancer arrays and the BPH arrays, autoantibody signa- tures were identified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined for the 27 antigens. RESULTS: Using the native antigen capture microarray plat- form, we found unique autoantibody signatures capable of distinguish- ing between prostate cancer and BPH. A SNR was calculated for each autoantibody reactivity on each array and compared. The top 5 auto- antibody signatures were found to react with TARDBP, TLN1, PARK7, PSIP1, and CALD1. Combining these antigens resulted in an AUC of 0.95 compared to 0.50 for PSA when differentiating between prostate cancer and BPH in our cohort. In addition, the coefficient of variance between duplicate runs for a given sample averaged 14.8% (range 11%–22%). CONCLUSIONS: Our results demonstrate the ability of a native antigen capture microarray platform to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with elevated PSA. Source of Funding: NIH, DoD, and Inanovate, Inc. 2326 ENGRAILED-2 (EN2): A URINARY BIOMARKER FOR THE DIAGNOSIS OF PROSTATE CANCER WITHOUT DRE Hardev Pandha*, Mohammed Ismail, Angie Boxall, Aagna Bhatt, Stephen Langley, Guildford, United Kingdom; Richard Hindley, Basingstoke, United Kingdom; Richard Morgan, Guildford, United Kingdom INTRODUCTION AND OBJECTIVES: Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. Recently described biomarkers are complex, expensive, often identify ‘high risk’ but are not immediately diagnostic and not easily adopted into clinical practice. We have assessed the diagnostic potential of EN2 protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men. Detection of EN2 was simple and inexpensive. e932 THE JOURNAL OF UROLOGY Vol. 185, No. 4S, Supplement, Wednesday, May 18, 2011