PD07-12 MOLECULAR PROFILING OF MULTI-FOCAL PROSTATE CANCER AND CONCOMITANT LYMPH NODE METASTASIS: IMPLICATIONS FOR TISSUE-BASED PROGNOSTIC BIOMARKERS

Abstract

You have accessJournal of UrologyProstate Cancer: Detection & Screening II1 Apr 2017PD07-12 MOLECULAR PROFILING OF MULTI-FOCAL PROSTATE CANCER AND CONCOMITANT LYMPH NODE METASTASIS: IMPLICATIONS FOR TISSUE-BASED PROGNOSTIC BIOMARKERS Simpa Salami, Daniel Hovelson, Romain Mathieu, Jeremy Kaplan, Martin Susani, Christopher Russell, Nathalie Rioux-Leclercq, Shahrokh Shariat, Scott Tomlins, and Ganesh Palapattu Simpa SalamiSimpa Salami More articles by this author , Daniel HovelsonDaniel Hovelson More articles by this author , Romain MathieuRomain Mathieu More articles by this author , Jeremy KaplanJeremy Kaplan More articles by this author , Martin SusaniMartin Susani More articles by this author , Christopher RussellChristopher Russell More articles by this author , Nathalie Rioux-LeclercqNathalie Rioux-Leclercq More articles by this author , Shahrokh ShariatShahrokh Shariat More articles by this author , Scott TomlinsScott Tomlins More articles by this author , and Ganesh PalapattuGanesh Palapattu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.387AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Current tissue-based prognostic biomarker assays claim that genetic assessment of a single focus is sufficient to predict disease behavior. We analyzed and compared the genetic profiles of multifocal prostate cancer (PCa) with concordant lymph node metastasis (LNM) to determine if expression based prognostic tests are robust to multifocality. METHODS This IRB-approved study comprised patients who underwent radical prostatectomy and lymph node dissection that revealed N1 disease or discordant multifocal disease (low- and high-grade foci). DNA and RNA were co-isolated from each tumor focus pre-identified on formalin fixed paraffin embedded specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the genetic and transcriptional signature of each sample, using the Oncomine Comprehensive (11 patients) or Comprehensive Cancer (DNA, 3 patients) Panels and a custom targeted RNAseq panel comprising genes for deriving prognostic signatures. RESULTS A total of 67 primary tumor and 17 LMN foci (with control tissue when available) from 14 patients were analyzed. We observed significant intra- and inter-patient molecular heterogeneity. For example, in patient #1, while all four regions of high-grade primary tumor showed TP53 somatic mutations and some broad copy number alterations (CNAs) with two samples from the LNM, tumor areas near the positive margin showed more complete concordance than intraprostatic regions. Critically, a low-grade primary tumor focus in this case showed no somatic mutation or CNA overlap with the high-grade or LNM samples. In patient #4, all tumor and LNM foci shared a large number of somatic mutations, including a frameshift mutation in PTEN, with no high level CNA identified, consistent with a hypermutated genotype. By targeted RNAseq, low-grade and high-grade tumors from the same patient showed distinct expression profiles using genes included in available prognostic signatures (Figure 1). CONCLUSIONS Our results challenge the claim that expression based prognostic tests are robust to multifocality. Additional molecular studies are needed to better characterize the biologically dominant lesion in multi-focal PCa and hold promise for the development of improved prognostic biomarkers. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e132-e133 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Simpa Salami More articles by this author Daniel Hovelson More articles by this author Romain Mathieu More articles by this author Jeremy Kaplan More articles by this author Martin Susani More articles by this author Christopher Russell More articles by this author Nathalie Rioux-Leclercq More articles by this author Shahrokh Shariat More articles by this author Scott Tomlins More articles by this author Ganesh Palapattu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...