2047 DECREASED LEVELS OF AGR2 AND INCREASED LEVELS OF CD10 IN PATIENTS WITH HIGH-STAGE PROSTATE CANCER PREDICT THE POOREST SURVIVAL

Abstract

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 20102047 DECREASED LEVELS OF AGR2 AND INCREASED LEVELS OF CD10 IN PATIENTS WITH HIGH-STAGE PROSTATE CANCER PREDICT THE POOREST SURVIVAL Alvin Liu, Emily Liebeskind, Erin Maresh, Steve Horvath, David Chia, and Lee Goodglick Alvin LiuAlvin Liu Seattle, WA More articles by this author , Emily LiebeskindEmily Liebeskind Seattle, WA More articles by this author , Erin MareshErin Maresh Los Angeles, CA More articles by this author , Steve HorvathSteve Horvath Los Angeles, CA More articles by this author , David ChiaDavid Chia Los Angeles, CA More articles by this author , and Lee GoodglickLee Goodglick Los Angeles, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2094AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES AGR2 expression is up-regulated in prostate cancer cells compared to luminal cells. CD10-positive cancer has a frequency of ∼30% and is correlated with poor outcome. Cancer cells show differential expression of these two genes. Could expression of these two genes be used to stratify prostate cancer? METHODS AGR2 expression was determined in isolated cancer cells by DNA array analysis and in tissue media by Western blot analysis. Expression of AGR2 and CD10 was analyzed on a tissue microarray (TMA) consisting of 246 cases of prostate cancer by immunohistochemistry. Protein expression was correlated with disease outcome, clinicopathological variables, and tumor recurrence following radical prostatectomy. Staining frequency and intensity of AGR2 or CD10 expression on the TMA was assessed. The percentage of glandular cell staining was scored from 0-100% and the intensity of staining was rated from 0 for below the level of detection to 3 for strong expression. An integrated measure of expression for frequency and intensity of staining was calculated using the following formula: [3(%x)+2(%y)+1(%z)]/100, where x, y, and z represented the percentage of cells staining at intensity 3, 2, and 1, respectively. For outcomes analysis, a mean pooled value for each case was determined. RESULTS Cancer cells isolated from a Gleason 3+3 tumor (G3) expressed 40-fold higher levels of AGR2 compared to luminal cells. AGR2 levels were increased in PIN lesions and cancer compared to BPH and normal (P<0.0001). Many fold higher level of the 17 kDa AGR2 protein was detected in prostate cancer compared to normal tissue. Cells isolated from a Gleason 4+4 tumor (G4) expressed about 10-fold less AGR2 compared to the G3 cells. Decreased AGR2 expression in high-stage (III and IV) prostate cancer predicted greater probability of recurrence (P=0.009). The median recurrence-free time in the lower AGR2 group was 14 mo compared to 38.5 mo in the group with relatively higher AGR2 expression. When CD10 expression was included, three high-stage groupings with regard to survival at 60 mo were: 100% AGR2hiCD10lo, 20% AGR2loCD10hi, and 50% AGR2loCD10lo and AGR2hiCD10hi (P=0.0247). Note luminal cells are AGR2–CD10+. CONCLUSIONS For high-stage patients where overall survival is poor, a small subset with tumors showing high AGR2 and low CD10 expression has low probability of disease recurrence. Thus, AGR2 and CD10 are useful biomarkers for stratification of prostate cancer. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e794-e795 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alvin Liu Seattle, WA More articles by this author Emily Liebeskind Seattle, WA More articles by this author Erin Maresh Los Angeles, CA More articles by this author Steve Horvath Los Angeles, CA More articles by this author David Chia Los Angeles, CA More articles by this author Lee Goodglick Los Angeles, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...