MP52-17 RECURRENT CHROMOSOMAL DELETIONS STATUS OBTAINED ON TISSUE CORES IS HIGHLY CORRELATED WITH LOCAL INVASIVE AND SYSTEMIC PROSTATE CANCER GROWTH

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research V1 Apr 2014MP52-17 RECURRENT CHROMOSOMAL DELETIONS STATUS OBTAINED ON TISSUE CORES IS HIGHLY CORRELATED WITH LOCAL INVASIVE AND SYSTEMIC PROSTATE CANCER GROWTH Meike Adam, Philipp Wenzel, Dominik Lanwehr, Pierre Tennstedt, Martina Kluth, Lia Burkhardt, Antje Krohn, Margit Fisch, Markus Graefen, Sarah Minner, Guido Sauter, Ronald Simon, and Thorsten Schlomm Meike AdamMeike Adam More articles by this author , Philipp WenzelPhilipp Wenzel More articles by this author , Dominik LanwehrDominik Lanwehr More articles by this author , Pierre TennstedtPierre Tennstedt More articles by this author , Martina KluthMartina Kluth More articles by this author , Lia BurkhardtLia Burkhardt More articles by this author , Antje KrohnAntje Krohn More articles by this author , Margit FischMargit Fisch More articles by this author , Markus GraefenMarkus Graefen More articles by this author , Sarah MinnerSarah Minner More articles by this author , Guido SauterGuido Sauter More articles by this author , Ronald SimonRonald Simon More articles by this author , and Thorsten SchlommThorsten Schlomm More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1627AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives A variety of chromosomal deletions are known to occur frequently in prostate cancer, but the clinical significance of most of these deletions is unknown. To learn more about epidemiology, associations with other molecular features, and relevance for key clinical endpoints, several recurrent deletions were analyzed on a large-scale tissue microarray platform. Methods A tissue microarray containing 11,156 prostate cancers was analyzed by fluorescence in situ hybridization (FISH) with dual-labeling probes including PTEN (10q23), TP53 (17p13.1), CHD1 (5q21) and MAP3K7 (6q15) together with their respective centromere probes. Patients were stratified into three major biological groups (organ confined, locally advanced, and systemic tumor growth) according to there multidimensional long-term follow up data. In addition, ERG fusion status and tumor cell proliferation (Ki67 labeling index) of all cancers were determined by immunohistochemistry. Results Deletions were seen for PTEN in 17.9% of 6,122, TP53 in 14.7% of 7,604, CHD1 in 9.9% of 7,026, and for MAP3K7 in 18.7% of 3,528 interpretable cases. All deletions were strongly linked to a positive (PTEN, TP53) or negative ERG status (CHD1, MAP3K7, p<0.0001 each) and early PSA recurrence. The combination of deletion information provided even better prognostic information, showing a dose dependent relationship between the number of deletions and the growth pattern (organ confined, local invasive, or systemic) of the tumor. Patients with no deletion had a 16.8% risk for local invasive and only 8.9% risk for systemic tumor growth, whereas the respective figures were 17.9% and 44.6% in patients with ≥ 3 deletions (p<0.001). The chance of having an organ confined tumor was 68.0% for patients with no deletion and 23.1% for patients with ≥ 3 deletions (p<0.001), respectively. Conclusions Our data show, that these analyzed chromosomal deletions are tightly linked with ERG status in prostate cancer and that the deletion status obtained on small tissue cores correlates with key biological tumor features. Combinatorial analysis of genomic alterations in prostate biopsies might provide clinically relevant information. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e586 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Meike Adam More articles by this author Philipp Wenzel More articles by this author Dominik Lanwehr More articles by this author Pierre Tennstedt More articles by this author Martina Kluth More articles by this author Lia Burkhardt More articles by this author Antje Krohn More articles by this author Margit Fisch More articles by this author Markus Graefen More articles by this author Sarah Minner More articles by this author Guido Sauter More articles by this author Ronald Simon More articles by this author Thorsten Schlomm More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...