2128 LOSS OF PTEN EXPRESSION IS AN INDEPENDENT PREDICTOR OF RECURRENCE IN PROSTATE CARCINOMA

Abstract

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 20102128 LOSS OF PTEN EXPRESSION IS AN INDEPENDENT PREDICTOR OF RECURRENCE IN PROSTATE CARCINOMA Luciana Schultz, Elizabeth Platz, Antoun Toubaji, Roula Albadine, Jessica Hicks, William Isaacs, Christian McEvoy, Alan Meeker, Angelo De Marzo, and George Netto Luciana SchultzLuciana Schultz More articles by this author , Elizabeth PlatzElizabeth Platz More articles by this author , Antoun ToubajiAntoun Toubaji More articles by this author , Roula AlbadineRoula Albadine More articles by this author , Jessica HicksJessica Hicks More articles by this author , William IsaacsWilliam Isaacs More articles by this author , Christian McEvoyChristian McEvoy More articles by this author , Alan MeekerAlan Meeker More articles by this author , Angelo De MarzoAngelo De Marzo More articles by this author , and George NettoGeorge Netto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2216AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate adenocarcinoma (PCa) shows genetic loss or mutation of at least one PTEN allele in approximately 30-70% of cases. PTEN loss is thought to play an early critical role in prostate oncogenesis possibly in cooperation with ERG oncogene activation. In the current study, we investigated the role of loss of PTEN expression in predicting disease recurrence in a well characterized nested case-control cohort of PCa which we have previously assessed for TMPRSS2-ERG fusion status. METHODS The cohort consisted of 8 TMAs containing paired tumor and normal tissues from radical prostatectomies (RRP) performed at our hospital between 1993 and 2001. They included 209 cases (recurred on follow up) and 209 controls (without PCa recurrence) that were tightly matched for Gleason grade, pTNM stage, ethnicity and patient age. Standard immunohistochemistry for PTEN (Cell Signalling) was performed. PTEN expression was assessed as percentage of cells staining (extent) and assigned an incremental (0 to 3+) intensity score. Additionally, an H-score was calculated as the product of intensity x extent. Prognostic interaction between PTEN expression, TMPRSS2-ERG fusion status and Chromosome 21 polyploidy (ERG gene locus) was evaluated. RESULTS Mean length of follow-up was 2.6 and 6.2 years in the case and control groups respectively. PTEN expression decreased with patient age (p=0.0002). PTEN extent of expression was significantly lower in pts with PCa recurrence compared to controls (p=0.02). The control group demonstrated a significantly higher intensity (2+ or 3+) of PTEN staining (p=0.05). Lack of PTEN expression, as well as low PTEN expression (extent <10%), was more frequently encountered in recurrent PCa (p<0.0001). However, the protective effect of PTEN expression was non-linear based on H-score levels. Concurrent TMPRSS2-ERG fusion had no additive effect to loss of PTEN in predicting PCa recurrence. Although tumors with concurrent Chromososme 21 polyploidy and PTEN loss were more likely to recur (OR:4.7) compared to those with PTEN loss alone (OR:3.2), the interaction between the two parameters was not synergistic in effect. CONCLUSIONS Lack of PTEN expression in PCa predicted higher likelihood of disease recurrence in our matched case-control cohort. A PTEN immunoexpression extent higher than 10% seems to exert a positive, albeit non-linear, effect on PCa outcome. We found no evidence of synergistic interaction between PTEN loss and presence of TMPRSS2-ERG fusion or between PTEN loss and Chromosome 21 polyploidy in predicting PCa recurrence. Baltimore, MD© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e827 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luciana Schultz More articles by this author Elizabeth Platz More articles by this author Antoun Toubaji More articles by this author Roula Albadine More articles by this author Jessica Hicks More articles by this author William Isaacs More articles by this author Christian McEvoy More articles by this author Alan Meeker More articles by this author Angelo De Marzo More articles by this author George Netto More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...