MP6-15 PTEN LOSS AND ERG EXPRESSION IN PROSTATE CANCER SURVIVAL

Abstract

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2015MP6-15 PTEN LOSS AND ERG EXPRESSION IN PROSTATE CANCER SURVIVAL Thomas Ahearn, Andreas Pettersson, Ericka Ebot, Travis Gerke, Carlos De Morais, Jessica Hicks, Kathryn Wilson, Jennifer Rider, Michelangelo Fiorentino, Stephen Finn, Edward Giovannucci, Massimo Loda, Meir Stampfer, Angelo De Marzo, Lorelei Mucci, and Tamara Lotan Thomas AhearnThomas Ahearn More articles by this author , Andreas PetterssonAndreas Pettersson More articles by this author , Ericka EbotEricka Ebot More articles by this author , Travis GerkeTravis Gerke More articles by this author , Carlos De MoraisCarlos De Morais More articles by this author , Jessica HicksJessica Hicks More articles by this author , Kathryn WilsonKathryn Wilson More articles by this author , Jennifer RiderJennifer Rider More articles by this author , Michelangelo FiorentinoMichelangelo Fiorentino More articles by this author , Stephen FinnStephen Finn More articles by this author , Edward GiovannucciEdward Giovannucci More articles by this author , Massimo LodaMassimo Loda More articles by this author , Meir StampferMeir Stampfer More articles by this author , Angelo De MarzoAngelo De Marzo More articles by this author , Lorelei MucciLorelei Mucci More articles by this author , and Tamara LotanTamara Lotan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.262AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, predominantly surgically-treated cohort. Moreover, PTEN loss is more common in TMPRSS2:ERG gene fusion-positive tumors, compared to fusion-negative tumors. Thus, presence of TMPRSS2:ERG gene fusion may modify the effects of PTEN loss on disease progression. We conducted a large patho-epidemiology investigation among prostate cancer patients in the Health Professional Follow-up Study and the Physicians' Health Study addressing: 1) the association of PTEN loss, assessed by a validated IHC protocol, with lethal progression, and 2) the potential for TMPRSS2:ERG gene fusion, detected by IHC, to modify the role of PTEN loss in lethal disease progression. METHODS In the Health Professionals Follow-Up Study and Physicians' Health Study, we followed 1045 incident prostate cancer cases diagnosed between 1986 – 2009 for cancer and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMA). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and BMI at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of the association with lethal disease. RESULTS On average men were followed 11.6 years, during which there were 81 lethal events. 16% of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss in a subset of cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR=1.9; 95% CI=1.2-3.0). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG negative (HR=2.8; 95% CI=1.5-5.2), but not ERG positive (HR=1.2; 95% CI=0.6-2.2) tumors. CONCLUSIONS PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e59-e60 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Thomas Ahearn More articles by this author Andreas Pettersson More articles by this author Ericka Ebot More articles by this author Travis Gerke More articles by this author Carlos De Morais More articles by this author Jessica Hicks More articles by this author Kathryn Wilson More articles by this author Jennifer Rider More articles by this author Michelangelo Fiorentino More articles by this author Stephen Finn More articles by this author Edward Giovannucci More articles by this author Massimo Loda More articles by this author Meir Stampfer More articles by this author Angelo De Marzo More articles by this author Lorelei Mucci More articles by this author Tamara Lotan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...