MP83-01 HIGH-GRADE PROSTATE CANCER HAS INCREASED MITOCHONDRIAL CONTENT

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II1 Apr 2017MP83-01 HIGH-GRADE PROSTATE CANCER HAS INCREASED MITOCHONDRIAL CONTENT Anton Kalsbeek, Eva Chan, Judith Grogan, Desiree Petersen, Weerachai Jaratlerdsiri, Ruta Gupta, Ruth Lyons, Anne-Maree Haynes, Lisa Horvath, James Kench, Phillip Stricker, and Vanessa Hayes Anton KalsbeekAnton Kalsbeek More articles by this author , Eva ChanEva Chan More articles by this author , Judith GroganJudith Grogan More articles by this author , Desiree PetersenDesiree Petersen More articles by this author , Weerachai JaratlerdsiriWeerachai Jaratlerdsiri More articles by this author , Ruta GuptaRuta Gupta More articles by this author , Ruth LyonsRuth Lyons More articles by this author , Anne-Maree HaynesAnne-Maree Haynes More articles by this author , Lisa HorvathLisa Horvath More articles by this author , James KenchJames Kench More articles by this author , Phillip StrickerPhillip Stricker More articles by this author , and Vanessa HayesVanessa Hayes More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2569AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer is marked by clinical and pathological heterogeneity. Therefore, there is a critical need to identify biomarkers that predict clinical presentation and outcomes. While much attention has been given to the nuclear genome, less emphasis has been placed on the maternally inherited, circular mitochondrial genome. Alterations in mitochondrial DNA (mtDNA) copy number are common in many human cancers, distinguishing cancer from normal tissue. In contrast, preliminary studies in prostate cancer, have shown no relative difference in mtDNA copy number between matched tumor-normal prostate cells, suggesting a possible field effect. The aim of this study was to test if there is a difference in mtDNA copy number between prostate cancer patients, that could be used to differentiate disease stage and clinical outcome. METHODS Fresh prostate cancer biopsies from 115 patients, with a median of 107 months clinical follow-up, were H&E stained and reviewed by pathologists for tumor grade and cellularity and marked for tumor excision. DNA was extracted from tumors and qPCR performed to establish relative mtDNA abundance. Multifocal biopsies were available and examined for seven of the patients. RESULTS Multivariate linear models revealed a significant correlation of decreasing mtDNA copy number with estimated sample tumor cellularity (p = 0.049*) and increasing with tumor pathology ISUP score (p = 0.007**), but no correlation with disease relapse (p = 0.60) or age (p = 0.71). Data from single patient multifocal biopsies showed a similar mtDNA content (average of 1.68-fold difference, range 1.01-2.48), compared to between patient mtDNA content (upper and lower interquartile range 3.23-fold difference, total range 15.99-fold variation) CONCLUSIONS We report a positive correlation between mtDNA count and tumor pathology score. Lack of variation in mtDNA abundance between molecular lesions within the same patients adds to accumulating evidence of a field effect contributing to the multifocal presentation of over 70% of prostate cancers. An increase in mtDNA copy number may therefore provide an ideal predictive tool for pathological stage irrespective of tumor purity during prostate diagnostic biopsy. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1105-e1106 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Anton Kalsbeek More articles by this author Eva Chan More articles by this author Judith Grogan More articles by this author Desiree Petersen More articles by this author Weerachai Jaratlerdsiri More articles by this author Ruta Gupta More articles by this author Ruth Lyons More articles by this author Anne-Maree Haynes More articles by this author Lisa Horvath More articles by this author James Kench More articles by this author Phillip Stricker More articles by this author Vanessa Hayes More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...