2108 PREOPERATIVE URINARY EXOSOME DETECTION OF TMPRSS2:ERG MRNA CLOSELY CORRELATES WITH TISSUE EXPRESSION AT RADICAL PROSTATECTOMY

Abstract

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 20122108 PREOPERATIVE URINARY EXOSOME DETECTION OF TMPRSS2:ERG MRNA CLOSELY CORRELATES WITH TISSUE EXPRESSION AT RADICAL PROSTATECTOMY Piruz Motamedinia, Anna Scott, Kendall Bate, Guillermo Salazar, Michael Lipsky, Neda Sadeghi, Wayne Comper, James McKiernan, and Leileata Russo Piruz MotamediniaPiruz Motamedinia New York, NY More articles by this author , Anna ScottAnna Scott New York, NY More articles by this author , Kendall BateKendall Bate New York, NY More articles by this author , Guillermo SalazarGuillermo Salazar New York, NY More articles by this author , Michael LipskyMichael Lipsky New York, NY More articles by this author , Neda SadeghiNeda Sadeghi New York, NY More articles by this author , Wayne ComperWayne Comper New York, NY More articles by this author , James McKiernanJames McKiernan New York, NY More articles by this author , and Leileata RussoLeileata Russo New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2276AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Exosomes (including microvesicles) are lipid bilayer vesicles that are released into biofluids such as urine and carry high integrity RNA from the parent cell. We have recently shown that urinary exosomes can be isolated and found to contain prostate specific mRNA transcripts. Here we examine the concordance of our detection of TMPRSS2:ERG (T:E) in urinary exosomes versus prostatectomy tissue and determine the rate of T:E detection in various prostate cancer related groups. METHODS Following Columbia University IRB approval, random urine samples (without prostate massage) were collected from 163 men who were stratified into 4 groups: TRUS prostate biopsy negative (Bx Neg, n=39), TRUS biopsy positive (Bx Pos, n=47), post-radical prostatectomy (RP, n=37) and controls (males <35 yrs, n=40). Additionally, whole-mount paraffin embedded prostate sections were obtained from 11 patients who underwent RP and had pre-RP urine specimens available (7 T:E positive, 4 T:E negative in pre-RP urine). Urine samples were stored at 4°C and 0.8 μm filtration was used to remove whole cells and debris. Urinary exosomal RNA and tissue RNA were isolated using an in-house technique (Exosome Diagnostics, NY) and analyzed using RP-qPCR. RESULTS Mean serum PSA levels were similar in the Bx Neg and Bx Pos groups. All groups except the control (males <35 yrs) were age matched. T:E fusion events were found to occur in 68% of Bx Pos and 44% of Bx Neg patients. Only 5% of controls expressed T:E and no patient in the post RP group had positive T:E detection. Furthermore, T:E expression was lost in the 4 Bx Pos patients that underwent prostatectomy and were retested following surgery. Tissue analysis revealed positive T:E in 8 of 11 prostates. T:E expression concordance between urine and tissue occurred in 10 of 11 (91%) patients with a sensitivity and specificity of 89% and 100%, respectively. CONCLUSIONS The detection rate of the T:E fusion in the Bx Pos group using urinary exosomal RNA was consistent with previous reports using tissue analyses. Our study exhibited near perfect concordance between urinary exosomal mRNA with matched prostate tissue analysis. The detection of T:E expression in the urine of patients with a negative TRUS biopsy may be due to false negative biopsy results or assay detection of T:E expression in premalignant lesions. The unique stability and yield of urinary exosomal RNA will broaden the role of exosomes in future diagnostic testing and simplify sample handing without the variability and patient discomfort inherent to prostate massage. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e850-e851 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Piruz Motamedinia New York, NY More articles by this author Anna Scott New York, NY More articles by this author Kendall Bate New York, NY More articles by this author Guillermo Salazar New York, NY More articles by this author Michael Lipsky New York, NY More articles by this author Neda Sadeghi New York, NY More articles by this author Wayne Comper New York, NY More articles by this author James McKiernan New York, NY More articles by this author Leileata Russo New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...