You have accessJournal of UrologyProstate Cancer: Basic Research (V)1 Apr 2013979 PREVALENCE AND PROGNOSTIC ROLE OF COMMON TUMOR SUPPRESSOR GENE DELETIONS IN PROSTATE CANCER Thorsten Schlomm, Martinia Kluth, Pierre Tennstedt, Guido Sauter, Lia Burkhardt, Anje Krohn, Jovisa Gjoni, Thomas Hass, Rami Galal, Ronald Simon, and Sarah Minner Thorsten SchlommThorsten Schlomm Hamburg, Germany More articles by this author , Martinia KluthMartinia Kluth Hamburg, Germany More articles by this author , Pierre TennstedtPierre Tennstedt Hamburg, Germany More articles by this author , Guido SauterGuido Sauter Hamburg, Germany More articles by this author , Lia BurkhardtLia Burkhardt Hamburg, Germany More articles by this author , Anje KrohnAnje Krohn Hamburg, Germany More articles by this author , Jovisa GjoniJovisa Gjoni Hamburg, Germany More articles by this author , Thomas HassThomas Hass Hamburg, Germany More articles by this author , Rami GalalRami Galal Hamburg, Germany More articles by this author , Ronald SimonRonald Simon Hamburg, Germany More articles by this author , and Sarah MinnerSarah Minner Hamburg, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.561AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A variety of chromosomal deletions are known to occur frequently in prostate cancer. Target genes and clinical significance of most of these deletions are unknown. To learn more about epidemiology, association with tumor phenotype, relevance for PSA recurrence and associations with other molecular features, several relevant deletions were analyzed on a large-scale tissue microarray platform in this project. METHODS For the purpose of this study, a tissue microarray containing 11,156 prostate cancers was analyzed by fluorescence in situ hybridization (FISH). All cancers were analyzed with dual-labeling probes including PTEN (10q23), TP53 (17p13.1), FOXP1 (3p14.1), CHD1 (5q21) and MAP3K7 (6q15) together with their respective centromere probes. 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, FOXP1 in 9.2% of 6,059, CHD1 in 9.9% of 7,026, and for MAP3K7 in 18.7% of 3,528 interpretable cases. All deletions were strongly linked to the ERG status (p<0.0001 each). In ERG positive/negative cancers, the deletion frequency was 27%/11% for PTEN, 22%/9% for TP53, 22%/7% for FOXP1, 6%/18% for CHD1, and 11%/28% for MAP3K7. The frequency of all these deletions increased significantly with tumor stage and grade. This was most prominently true for TP53, PTEN and MAP3K7 (p<0.0001 each). In addition, there was a significant association of most deletions with the likelihood of PSA recurrence (PTEN, TP53, MAP3K7, CHD1: p<0.0001; FOXP1: p=0.1486). The combination of deletion information provided even better prognostic information. There was a dose dependent relationship between the number of deletions and PSA recurrence. Tumors with no deletion had the best clinical outcome followed by cancers, with one, two, and three or more deletions (p<0.0001). Particular strong prognostic information was obtained by combining PTEN and p53 deletions. Patients with none of these alterations had 17% PSA recurrence while the respective figure was 40% on patients with both deletions. CONCLUSIONS In summary, these data show, that chromosomal deletions are tightly linked with ERG status in prostate cancer and that most of these deletions have clinical relevance. Combinatorial analysis of genomic alterations in prostate cancer might provide clinically relevant information. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e402 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Thorsten Schlomm Hamburg, Germany More articles by this author Martinia Kluth Hamburg, Germany More articles by this author Pierre Tennstedt Hamburg, Germany More articles by this author Guido Sauter Hamburg, Germany More articles by this author Lia Burkhardt Hamburg, Germany More articles by this author Anje Krohn Hamburg, Germany More articles by this author Jovisa Gjoni Hamburg, Germany More articles by this author Thomas Hass Hamburg, Germany More articles by this author Rami Galal Hamburg, Germany More articles by this author Ronald Simon Hamburg, Germany More articles by this author Sarah Minner Hamburg, Germany More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...