MP55-08 GENOMIC DELETION OF CHROMOSOME 12P IS AN INDEPENDENT PROGNOSTIC MARKER IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research III1 Apr 2015MP55-08 GENOMIC DELETION OF CHROMOSOME 12P IS AN INDEPENDENT PROGNOSTIC MARKER IN PROSTATE CANCER Raisa Pompe, Martina Kluth, Sarah Minner, Philipp Gild, Ronald Simon, Pierre Tennstedt, Markus Graefen, Guido Sauter, and Thorsten Schlomm Raisa PompeRaisa Pompe More articles by this author , Martina KluthMartina Kluth More articles by this author , Sarah MinnerSarah Minner More articles by this author , Philipp GildPhilipp Gild More articles by this author , Ronald SimonRonald Simon More articles by this author , Pierre TennstedtPierre Tennstedt More articles by this author , Markus GraefenMarkus Graefen More articles by this author , Guido SauterGuido Sauter More articles by this author , and Thorsten SchlommThorsten Schlomm More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2051AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Deletion of 12p is a recurrent alteration in prostate cancer, but the prevalence and clinical consequences of this alteration have not been studied in detail. METHODS Dual labeling fluorescence in situ hybridization (FISH) using probes for 12p13 (CDKN1B; p27) and for centromere 12 as a reference was used to analyze more than 7,000 prostate cancers with clinical follow-up data assembled in a tissue microarray (TMA) format. CDKN1B was selected as a probe because it is located in the center of the deletion, which, however, spans >10 Mb and includes >50 genes in 80% of cancers with 12p deletion. Results were compared to clinically follow-up data, ERG status and p27 protein expression in univariate und multivariate analyses. RESULTS Deletion of 12p was found in 13.7% of cancers and included 13.5% hemizygeous and 0.2% homozygeous deletions. 12p deletion were linked to advanced tumor stage (p<0.0001), high Gleason grade (p<0.0001), lymph node metastasis (p=0.0004), rapid tumor cell proliferation (p<0.0001), and early biochemical recurrence (BCR) (p=0.0027). Multivariate cox regression analysis including pT stage (p<0.0001), Gleason grade (p<0.0001), pN status (p=0.0001), preoperative PSA levels (p=0.0001), and resection margin status (p=0.0001) revealed an independent prognostic value of 12p deletion (p=0.0014). Deletion of 12p was unrelated to the ERG fusion status. Deletion of 12p was only marginally linked to reduced p27 expression, which by itself was unrelated to clinical outcome. This argues against p27 as the key target gene of 12p deletions. As none of the involved 12p genes is recurrently mutated in next generation sequencing studies, simultaneous dosage reduction of multiple genes may exert a relevant biological effect in 12p deleted cancers. CONCLUSIONS The results of our study demonstrate that 12p deletion is frequent in prostate cancer and provides independent prognostic information. 12p deletion analysis alone, or in combination with other prognostic parameters may thus have clinical utility. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e675-e676 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Raisa Pompe More articles by this author Martina Kluth More articles by this author Sarah Minner More articles by this author Philipp Gild More articles by this author Ronald Simon More articles by this author Pierre Tennstedt More articles by this author Markus Graefen More articles by this author Guido Sauter More articles by this author Thorsten Schlomm More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...