EMBARGOED FOR RELEASE UNTIL MONDAY, MAY 16, 2011 AT 1:00 P.M.                                                             ...
resulted in the highest sensitivity and diagnostic accuracy. Using TMPRSS2:ERG in addition to PCA3 added onlyone false pos...
Pre-Operative Urinary Prostate Cancer Gene 3 (PCA3) is Predicting Pathologically Confirmed Small Volumeand Insignificant P...
715GENETIC RISK VARIANTS ON 8Q24 ASSOCIATED WITH PROSTATE CANCER AGGRESSIVENESSBrian T. Helfand, Matthias D. Hofer, Qiaoya...
1616RATIONAL BASIS FOR THE COMBINATION OF PCA3 AND TMPRSS2:ERG GENE FUSION INPROSTATE CANCER DIAGNOSISGregoire Robert, San...
2289GENETIC POLYMORPHISMS OF CYP17A1 MAY PREDICT EARLY PROGRESSION AFTER PRIMARYANDROGEN DEPRIVATION THERAPY IN JAPANESE M...
2319A TMPRSS2:ERG GENE FUSION MOLECULAR URINE ASSAY CORRELATES WITH PATHOLOGIC STAGE ANDPROSTATECTOMY GLEASON SCORE AND IS...
2325AUTOANTIBODY SIGNATURES AS BIOMARKERS TO DISTINGUISH PROSTATE CANCER FROM BENIGNPROSTATIC HYPERPLASIA USING A NATIVE A...
1362DETECTION AND IDENTIFICATION OF A MIRNA EXPRESSION PROFILE FROM CELL-FREE URINE: POTENTIALUTILITY IN BLADDER CANCERJes...
187PRE-OPERATIVE URINARY PROSTATE CANCER GENE 3 (PCA3) IS PREDICTING PATHOLOGICALLY CONFIRMEDSMALL VOLUME AND INSIGNIFICAN...
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5.16.11 biomarkers and genetic tests

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5.16.11 biomarkers and genetic tests

  1. 1. EMBARGOED FOR RELEASE UNTIL MONDAY, MAY 16, 2011 AT 1:00 P.M. Contact: Wendy Waldsachs Isett, AUA 410-977-4770, wisett@AUAnet.orgBUILDING A BETTER CANCER TEST: UPDATES ON NEW BIOMARKERS AND GENETIC ASSAYS FOR BLADDER AND PROSTATE CANCERSWashington, DC, May 16, 2010—Clinicians treating bladder and prostate cancers face significant challenges notonly in treating, but also diagnosing these diseases. Diagnostic tests are limited, and, in some cases, the tests’ability to distinguish indolent vs. aggressive disease is questionable. New research on genetic tests andbiomarkers for disease, being presented during the 2011 Annual Meeting of the American Urological Association(AUA), holds the promise for newer, better tests for these cancers. The studies will be presented to the pressduring a special session on Monday, May 16, 2011 at 1:00 p.m. in the AUA Press Suite. The session will bemoderated by AUA Public Media Committee Chair Anthony Y. Smith, MD.Studies being presented include:Genetic Risk Variants On 8q24 Associated with Prostate Cancer Aggressiveness (#715): Certain genetic allelesassociated with prostate cancer risk may also be connected to aggressive pathology features and may predicthigher Gleason-grade disease in some men, according to researchers at Northwestern University. Genotypes forcertain previously reported risk alleles were determined for more than 900 men with Gleason 6 prostate cancerswho had undergone radical prostatectomy, and authors compared allele frequency for men whose tumors wereultimately upgraded to a pathologic Gleason 7 and those whose final pathologic Gleason was 6. Those with riskalleles on chromosomes 8q24 and 19q13 were 1.7 and 2.7 times more likely to be upgraded in the finalpathology tumor specimen, suggesting that certain genotypes may be a strong predictor of aggressive pathologyfeatures.Rational Basis for the Combination of PCA3 and TMPRSS2:ERG Gene Fusion in Prostate Cancer Diagnosis(#1616): According to new data from Radboud University Nijmegen Medical Center in the Netherlands,measuring TMPRSS2:ERG expression in addition to PCA3 may improve the sensitivity and accuracy of the PCA3test for prostate cancer. Using tissue samples for benign prostatic hyperplasia (48 samples) and prostate cancer(48 samples), as well as normal prostate tissue (32 samples), authors measured PCA3 and TMPRSS2:ERGexpression. The PCA3 test had a sensitivity of 84.4 for prostate cancer, but included one false-positive and sevenfalse-negative samples. The TMPRSS2:ERG gene fusion test was positive in 8.3 percent of the BPH samples, 15.6percent of the normal tissue samples and half the prostate cancer samples. However, combining both tests
  2. 2. resulted in the highest sensitivity and diagnostic accuracy. Using TMPRSS2:ERG in addition to PCA3 added onlyone false positive, and eliminated four of the seven false negatives seen with PCA3 alone.Genetic Polymorphisms of CYP17A1 May Predict Early Progression after Primary Androgen DeprivationTherapy in Japanese Men with Prostate Cancer (#2289): Certain genetic polymorphic variations may allowphysicians to predict a patient’s sensitivity to hormonal therapy to treat prostate cancer, according to newresearchers in Japan, who examined a possible correlation between certain single nucleotide polymorphisms(SNPs) from eight genes involved in androgen synthesis and metabolism and a man’s progression to castration-resistant disease. The period from diagnosis to data collection was 43 months. In this study, which included 214patients, researchers compared the association of genotypes to the efficacy of androgen deprivation therapy,and found that patients with SNP rs6162 on the CYP17A1 gene were more likely to experience cancerprogression following androgen deprivation therapy.A TMPRSS2:ERG Gene Fusion Molecular Urine Assay Correlates with Pathologic Stage and ProstatectomyGleason Score and is Associated with Biopsy-to-Prostatectomy Gleason Upgrading (#2319): Researchers inGermany and the United States will present data on a new quantitative TMPRSS2:ERG gene fusion urine assay topredict outcomes in men with prostate cancer scheduled for radical prostatectomy. Researchers obtained urinespecimens from men to assess TMPRSS2:ERG levels prior to surgery, and compared these levels with post-surgery pathologic findings. Of the 74 men, 28 had non-organ confined disease, and 69 had a Gleason score of 7or greater. 21 patients with biopsy Gleason 6 disease were upgraded to a pathologic Gleason grade of 7 orgreater. Median TMPRSS2:ERG score was significantly higher in men with non-organ confined disease comparedto those who had organ-confined disease (80 vs. 9). Median TMPRSS2:ERG scores for patients with pathologicalupgrading was 32, compared to 2 for those whose Gleason scores were not upgraded.Autoantibody Signatures as Biomarkers to Distinguish Prostate Cancer from Benign Prostatic Hyperplasiausing a Native Antigen Capture Microarray Platform (#2325): A common criticism of the prostate-specificantigen (PSA) test is its lack of specificity in differentiating between benign prostatic hyperplasia (BPH) andprostate cancer. Through the use of a customized array platform, researchers at Brigham and Women’s Hospitaland Northeastern University have identified five autoantibody signatures to specific cancer targets that, whenthe antigens were combined, were more effective than the PSA test in distinguishing between benign andmalignant disease.Detection and Identification of a miRNA Expression Profile from Cell-Free Urine: Potential Utility in BladderCancer (#1362): Micro ribonucleic acid (miRNA) molecules, previously shown to play a key role in tumorigenesis,can play a promising role in diagnosing and treating cancers. Researchers from the Lahey Clinic in Bostonexamined the role that miRNA might play in diagnosing bladder cancer. Using urine from patients withconfirmed bladder cancer and control patients with no history of cancer, authors isolated cell-free RNA from 35healthy control patients and 142 patients with bladder cancer, and profiled 730 miRNAs. Disease progressioncorrelated with the number of miRNAs expressed, with healthy controls expressing 8 miRNAs and patients with>T2 carcinoma expressing 228 miRNAs. Individual samples revealed an increase with some miRNA as diseaseprogressed, suggesting that miRNA profiling could be of future clinical value in the treatment of bladder cancer.
  3. 3. Pre-Operative Urinary Prostate Cancer Gene 3 (PCA3) is Predicting Pathologically Confirmed Small Volumeand Insignificant Prostate Cancer (#187): PCA3 has demonstrated success in identifying patients with prostatecancer; however, new data from the Medical University of Graz in Austria suggests that the test may be avaluable predictor of low-volume disease and may have a future role in managing patients on active surveillanceprotocols. Using pre-operative PCA3 scores and tumor volume data from 160 patients, authors used logisticregression models to identify endpoints for low-volume disease (less than 0.5 ml) and insignificant disease (usingEpstein criteria). Low tumor volume and pathologically insignificant prostate cancer were present in 21.2percent (n=34) and 10 percent (n=16) of patients. In those patients with low-volume and/or insignificantdisease, PCA3 scores were significantly lower.“The critical piece of the puzzle that is missing right now for treatment of a number of urologic cancers, butparticularly for prostate cancer, are biomarkers that can be used to tell us prior to treatment which patientsharbor slow growing indolent cancers, which harbor cancers that we might have a shot at curing and whichharbor cancers that are so aggressive that they require a systemic approach,” Dr. Smith said.NOTE TO REPORTERS: Experts are available to discuss this study outside normal briefing times. To arrange aninterview with an expert, please contact the AUA Communications Office at the number above or e-mailwisett@AUAnet.org.About the American Urological Association: Founded in 1902 and headquartered near Baltimore, Maryland, the AmericanUrological Association is the pre-eminent professional organization for urologists, with more than 17,000 membersthroughout the world. An educational nonprofit organization, the AUA pursues its mission of fostering the highest standardsof urologic care by carrying out a wide variety of programs for members and their patients. ###
  4. 4. 715GENETIC RISK VARIANTS ON 8Q24 ASSOCIATED WITH PROSTATE CANCER AGGRESSIVENESSBrian T. Helfand, Matthias D. Hofer, Qiaoyan Hu, Barry B. McGuire, Daniel C. OBrien, William J. Catalona,Chicago, ILINTRODUCTION AND OBJECTIVES: Genome wide association studies have identified that a striking set ofprostate cancer (CaP) risk alleles are clustered within a large gene desert on chromosome 8q24. To date, morethan 8 different risk alleles have been mapped to this region. Our prior studies conducted in relatively smallpopulations of men have suggested that a few of these alleles are associated with aggressive pathology (e.g.Helfand et al. J Urol, 2008;179: 2197). However, the collective influence of many of the 8q24 alleles onaggressiveness in large populations remains to be determined.METHODS: 1376 Caucasian men underwent radical prostatectomy from March 2003 to September 2009 at ourinstitution and were genotyped for 5 different risk alleles located on chromosome 8q24. The associationsbetween allele frequency, carrier status and adverse clinico-pathologic features were compared. Aggressivedisease was defined as pathologic Gleason score ?4+3 and/or pathologic tumor stage ?3b. Possible clinicallyinsignificant disease was defined using Ohori criteria: organ-confined, tumor volume <0.5cc, and no Gleasongrade 4 (Goto et al. J Urol, 1996; 156: 1059).RESULTS: 3 of the 5 8q24 risk alleles were present at higher frequencies in men with aggressive disease (Table1). There was a significantly higher proportion of carriers of the 8q24 risk allele, SNP rs16902094, withaggressive disease compared to non-aggressive disease (44.2% vs. 28.4%, p <0.001). In addition, there was asignificantly lower proportion of carriers of this allele with ?insignificant? disease compared to ?significant?disease (31.4% vs. 16.9%; p=0.01). Location SNP Non-Aggressive (%) N=1123 Aggressive (%) N=253 P value 8q24 rs16901979 11.8 9.1 0.23 8q24 rs16902094 28.4 44.2 <0.001 8q24 rs445114 89.1 93.7 0.03 8q24 rs6983267 80.4 83.0 0.34 8q24 rs1447295 25.6 22.1 0.26CONCLUSIONS: Risk alleles on chromosome 8q24 are associated with PCa susceptibility and aggressiveness.Specifically, the rs16902094 allele significantly increase the risk of aggressive disease. Future confirmatorystudies in other populations are warranted.Source of Funding: Supported in part by the Urological Research Foundation, Prostate SPORE grant (P50CA90386-05S2) and the Robert H. Lurie Comprehensive Cancer Center Grant (P30 CA60553)
  5. 5. 1616RATIONAL BASIS FOR THE COMBINATION OF PCA3 AND TMPRSS2:ERG GENE FUSION INPROSTATE CANCER DIAGNOSISGregoire Robert, Sander Jannink, Tilly Aalders, Peter Mulders, Jack Schalken, Bordeaux, FranceINTRODUCTION AND OBJECTIVES: The prostate cancer gene 3 (PCA3) and TMPRSS2:ERG genefusion are promising prostate cancer (PCa) specific biomarkers. Our aim was to simultaneouslyquantify the expression levels of PCA3 and TMPRSS2:ERG in a large panel of benign prostatichyperplasia (BPH), normal prostate adjacent to PCa (NP) and PCa tissue samples, to provide arational basis for the understanding of the false-positive and false-negative results of the urineassays.METHODS: The tissue samples were carefully histopathologically characterized to obtainhomogeneous groups. The mRNA was isolated, transcribed into cDNA and the expressions ofPCA3 and TMPRSS2:ERG were measured using a quantitative real-time polymerase chainreaction. The relative expression levels of the markers were normalized for the housekeepinggene HPRT and were compared between the different groups.RESULTS: We included 48 BPH, 32 NP and 48 PCa. The PCA3 test had a sensitivity of 85.4% butled to the identification of 1 false-positive and 7 false-negative samples. The TMPRSS2:ERG genefusion test was positive in 8.3% of the BPH, 15.6% of the NP and 50% of the PCa samples. Wehad to define a cut-off value to avoid 8 false-positive results with the TMPRSS2:ERG test. Thecombination of the PCA3 test with the TMPRSS2:ERG test had the highest sensitivity and thebest diagnostic accuracy. In case of a negative PCA3 test, the addition of the TMPRSS2/ERG testallowed to diagnose 4 of the 7 false-negative samples and added only 1 false-positive.First Line Second Line Se (%) Sp (%) Youden IndexPCA3 - 85.4 98.7 0.84TMPRSS2:ERG - 45.8 98.75 0.45PCA3 + TMPRSS2:ERG - 91.7 97.5 0.89PCA3 TMPRSS2:ERG 93.75 97.5 0.9For PCA3, the cut-off value was 19.6; For TMPRSS2 :ERG, the cut-off value was 2.71CONCLUSIONS: Most of the false-negative results of the PCA3 test were corrected by thecombination with TMPRSS2:ERG (57%). The combination had a higher sensitivity and a betteraccuracy. Some of the control samples did express TMPRSS2:ERG and a cut-off value had to bedefined to avoid false-positive results.Source of Funding: Grégoire Robert was granted by the EAU scholarship Program and by theFrench Urological Association (AFU)
  6. 6. 2289GENETIC POLYMORPHISMS OF CYP17A1 MAY PREDICT EARLY PROGRESSION AFTER PRIMARYANDROGEN DEPRIVATION THERAPY IN JAPANESE MEN WITH PROSTATE CANCERMasashi Nakayama, Takeshi Yamada, Tomohito Shimizu, Shinpei Nonen, Kensaku Nishimura,Kazuo Nishimura, Tsuneo Hara, Go Tanigawa, Toshiaki Yoshioka, Koji Hatano, Yasutomo Nakai,Hitoshi Takayama, Yasushi Fujio, Junichi Azuma, Akihiko Okuyama, Norio Nonomura, Osaka-city,Osaka, JapanINTRODUCTION AND OBJECTIVES: The androgen deprivation therapy with LH-RH analoguesand/or anti-androgen is the standard therapy for advanced prostate cancer. However, there is alarge individual difference in the efficacy of the therapy. It is difficult to predict the duration ofresponse to the hormonal therapy. In this study, we have examined whether geneticpolymorphic variation can explain the sensitivity to hormonal therapy in Japanese patients.METHODS: Two hundred fourteen patients with prostate cancer, primary treated with androgendeprivation therapy, were enrolled into this study. The median observation period fromdiagnosis to data collection was 43 months. We divided the subjects into three groups (I-III);Group I, ninety five patients who progressed to CRPC earlier than 43 months (high risk patients):Group II, eighty five patients who remained stable disease even after 43 months (low riskpatients): Group III, thirty four patients who exhibited stable disease condition with theirobservation less than 43 months (short-period observation). We excluded the data of Group IIIfrom the data set, and compared the association of genotypes with the efficacy to androgendeprivation therapy in Groups I and II (high risk and low risk populations). We have selected 22single nucleotide polymorphisms (SNPs) from 8 genes involved in androgen synthesis andmetabolism that are CYP17A1, HSD3B1, SRD5A1, SRD5A2, HSD17B3, CYP1B1, CYP 11A, andCYP24A which is involved in metabolism of activated Vitamin D. The SNPs were assayed byprimer extension method. Logistic regression method, with adjustments for age, clinical diseasestage and Gleason score at diagnosis, was applied for the analysis.RESULTS: The median observation period from diagnosis to data collection was 43 months. Weobserved statistical significance for rs743572 A > G (p=0.01, OR (Odds-Ratio) 0.30, 95%CI 0.12-0.79), rs6162 G >A (p=0.01, OR 3.33, 95% CI 1.27-8.72), rs6163 C > A (p=0.01, OR 3.33, 95% CI1.27-8.72) and rs1004467 T > C (p=0.04, OR 2.43, 95%CI 1.03-5.73) in CYP17A1. There was nosignificant difference in SNPs of other genes between two groups.CONCLUSIONS: Although larger validation study is needed, our study suggests that geneticpolymorphisms in CYP17A1 are expected as good predictors for risk of progression in Japaneseprostate cancer patients receiving androgen deprivation therapy.Source of Funding: none
  7. 7. 2319A TMPRSS2:ERG GENE FUSION MOLECULAR URINE ASSAY CORRELATES WITH PATHOLOGIC STAGE ANDPROSTATECTOMY GLEASON SCORE AND IS ASSOCIATED WITH BIOPSY-TO-PROSTATECTOMY GLEASONUPGRADINGAlexander Haese, Felix Chun, Sarah Meyer, Sheila Aubin, John Day, Jack Groskopf, Hamburg, GermanyINTRODUCTION AND OBJECTIVES: An unmet need in PCa prognosis is the differentiation between indolent andsignificant PCa. Biochemical (e.g. PSA), clinical (e.g. clinical stage) or histological (BxGleason score) parameters,alone or combined, are not sufficiently accurate to aid in this critical distinction. On a genetic basis, a fusionbetween TMPRSS2 and the ETS family of transcription factors, found in 50-70% of PCa, is the most commonspecific gene rearrangement identified to date among solid human malignancies. Studies have linked PCa genefusions to indicators of significant PCA. In this prospective, ongoing study, we evaluated the correlation of aprototype quantitative TMPRSS2:ERG (T2:ERG) gene fusion urine assay with outcomes in men with PCascheduled for RRPMETHODS: Post-DRE first-catch urine specimens were collected prior to RRP. T2:ERG mRNA copies werequantified using a transcription-mediated amplification assay and results normalized to PSA mRNA copies bycalculating the ratio of TMPRSS2:ERG/PSA copies x 100,000 (T2:ERG Score). The prototype T2:ERG urine assaydetects the gene fusion mRNA isoform corresponding to TMPRSS2 exon 1 to ERG exon 4. The T2:ERG Score wascorrelated with the presence or absence of pathologically organ (OC) vs. non-organ-confined (NOC) PCa and thepresence or absence of Bx-to-RRP Gleason upgrading.RESULTS: Of 74 subjects 28 (38%) had NOC-disease (?pT3) and 69 (93%) had a RRP Gleason score ?7. 21/26subjects with BxGleason score of 6 were upgraded to Gleason Score ?7 at RRP. Median T2:ERG Score wassignificantly higher in men with NOC vs. OC-PCa (80 vs. 9, p=0.002) and with RRP Gleason scores ?7 vs. 6 (31 vs.2, p=0.04). The median T2:ERG Score for subjects with vs without Bx-to-RRP-upgrading was 32 vs 2, respectively.CONCLUSIONS: The T2:ERG assay correlated significantly with pT-stage and RRPGleason score. Interestingly,subjects with Bx-to-RRP-upgrading showed a trend towards higher median T2:ERG Scores. These data suggestthat a T2:ERG urine assay may be useful to decide when more aggressive treatment of PCa is necessary.Source of Funding: none
  8. 8. 2325AUTOANTIBODY SIGNATURES AS BIOMARKERS TO DISTINGUISH PROSTATE CANCER FROM BENIGNPROSTATIC HYPERPLASIA USING A NATIVE ANTIGEN CAPTURE MICROARRAY PLATFORMDennis ORourke, Daniel DiJohnson, Michael OLeary, Jerome Richie, Brian Liu, Boston, MA INTRODUCTION AND OBJECTIVES: Serum prostate specific antigen (PSA) levels lack the specificity todifferentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We nowreport the identification of 5 autoantibody signatures to specific cancer targets which may be capable of rulingout a diagnosis of cancer for patients with non-malignant prostatic disease, such as BPH, in patients withelevated serum PSA.METHODS: To discover new biomarkers which may distinguish between prostate cancer and BPH, a nativeantigen capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayedonto nano-particle slides to capture native antigens from prostate cancer cells. Using the immobilized antigensas baits, autoantibodies from prostate cancer patients and patients with BPH can be isolated and probed. Frompreliminary experiments using an initial set of over 500 cancer related antigens, a customized array containing27 unique antigens was further tested. Prostate cancer patient (n=41) and BPH patient serum samples with amean follow-up of 6.8 years without the diagnosis of cancer (n=39) were obtained. 100ug of IgGs were purifiedand dye labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and theintensity was quantified. For each spot, a signal-to-noise ratio (SNR) was measured to eliminate backgroundinterference. Through comparative analysis of the prostate cancer arrays and the BPH arrays, autoantibodysignatures 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 platform, we found unique autoantibody signaturescapable of distinguishing between prostate cancer and BPH. A SNR was calculated for each autoantibodyreactivity on each array and compared. The top 5 autoantibody 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 PSAwhen differentiating between prostate cancer and BPH in our cohort. In addition, the coefficient of variancebetween 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 identifyspecific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in thereduction of unnecessary biopsies in patients with elevated PSA.Source of Funding: NIH, DoD, and Inanovate, Inc.
  9. 9. 1362DETECTION AND IDENTIFICATION OF A MIRNA EXPRESSION PROFILE FROM CELL-FREE URINE: POTENTIALUTILITY IN BLADDER CANCERJessica DeLong, Niall Harty, Spencer Kozinn, Ian Summerhayes, John Libertino, Kimberly Rieger-Christ, Brookline,MAINTRODUCTION AND OBJECTIVES: MicroRNAs are small, non-coding RNAs that have been shown to play animportant role in tumorigenesis. There is differential expression of miRNA in cancer progression, and profiling ofmiRNA is promising for both diagnosis and treatment of malignant tumors. In this study we isolated RNA fromcell-free urine in an attempt to characterize miRNA profiles indicating the presence of urothelial carcinoma andits potential use as a non-invasive assay to identify patients with cancer progression.METHODS: Urine was collected from patients diagnosed with bladder cancer and control patients with nohistory of cancer under an IRB-approved protocol. Specimens were then centrifuged and total RNA was isolatedfrom the supernatants using the mirVana Paris? kit. A total of 178 samples were grouped according to grade andstage: healthy controls (35), TaG1 (19), T1G3 (16), ?T2 (30), carcinoma in situ (CIS; 28) and no evidence ofdisease following therapy (50). Seven hundred and thirty miRNAs were profiled by qRT-PCR on pooled sampleswithin each group. Validation of selected miRNAs was performed on individual samples using qRT-PCR.RESULTS: Cell-free RNA was isolated from urine of 35 healthy controls and 143 patients with bladder cancer. Ofthe 730 miRNAs tested, 236 were detected in at least one of the pooled samples using a cycle threshold cutoffof 35. The number of miRNAs detected in the pooled samples correlated with disease progression where thehealthy control group and the ?T2 group expressed 8 and 228 miRNAs, respectively. qRT-PCR of individualsamples revealed a gradual increase of some miRNAs with disease progression. Statistical analysis adjusted formultiple comparisons demonstrated differences between groups based on miRNA expression levels. In addition,a panel of miRNAs was identified which discriminated between cancer and cancer-free patients.CONCLUSIONS: This study demonstrates the successful isolation of miRNAs from cell-free urine. Utilizing non-invasive urine based assays, we identified a miRNA panel that can discriminate cancer-free patients and patientswith urinary carcinoma of the bladder. These findings provide evidence that profiling of miRNAs from cell-freeurine holds the promise for the development of valuable clinical tools.Source of Funding: None.
  10. 10. 187PRE-OPERATIVE URINARY PROSTATE CANCER GENE 3 (PCA3) IS PREDICTING PATHOLOGICALLY CONFIRMEDSMALL VOLUME AND INSIGNIFICANT PROSTATE CANCERMarco Auprich, John F. Ward, Richard Babaian, Karl Pummer, Herbert Augustin, Ferdinand Luger, Stefan Gutschi,Hartwig Huland, Alexander Haese, Graz, Austria INTRODUCTION AND OBJECTIVES: Prostate CAncer Gene 3 (PCA3) score was recently identified to predict smallvolume [tumor volume (TV) < 0.5ml] and pathologically insignificant prostate cancer (IPCa) prior to RP. Objectivewas to evaluate PCA3?s potential to improve the multivariable accuracy in the prediction of pathological TV<0.5ml and IPCa in a US-European cohortMETHODS: Complete retrospective clinical and pathological data of consecutive RP men form two two referralcentres including pre-operative PCA3 scores and computerized-assisted planimetrically measured tumor volumedata were available in 160 patients. PCA3 scores were assessed using the Progensa assay®. Beyond standard riskfactors (age, DRE, PSA, prostate volume, biopsy Gleason score, percent positive cores), five different PCA3codings (continuously and cut-off 17, 24, 35, 47) were used in logistic regression models to identify five distinctpathological endpoints: a) low volume disease (<0.5ml), b) insignificant PCa according to the Epstein criteria.Accuracy estimates of each endpoint were quantified using the area under the curve (AUC) of the receiveroperator characteristic (ROC) analysis in models with and without PCA3.RESULTS: Tumor volume <0.5 ml and pathological IPCa was present in 21.2% (n=34) and 10% (n=16) of patients.PCA3 scores were significantly lower in low volume disease and insignificant PCa (p?0.001). AUC ofmultivariable low volume disease (+2.4 to +5.5%) and insignificant PCa-models (+3 to +3.9%) increased whenPCA3 was added to standard clinical risk factors.CONCLUSIONS: PCA3 was confirmed as valuable predictor of pathologically confirmed low volume disease andinsignificant PCa. Further exploration of its role as an additive marker to select patients for active surveillancemay be warrantedSource of Funding: none

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