895 ESTROGEN RECEPTOR BETA EXPRESSION AND PHARMACOLOGIC TARGETING IN TRANSITIONAL CELL CARCINOMA OF THE BLADDER (2012)

You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2012895 ESTROGEN RECEPTOR BETA EXPRESSION AND PHARMACOLOGIC TARGETING IN TRANSITIONAL CELL CARCINOMA OF THE BLADDER Eric Kauffman, Brian Robinson, Martin Downes, Katarzyna Marcinkiewicz, Leagh Powell, Ming Ming Lee, Douglas Scherr, Lorraine Gudas, and Nigel Mongan Eric KauffmanEric Kauffman Bethesda, MD More articles by this author , Brian RobinsonBrian Robinson New York, NY More articles by this author , Martin DownesMartin Downes Dublin, Ireland More articles by this author , Katarzyna MarcinkiewiczKatarzyna Marcinkiewicz New York, NY More articles by this author , Leagh PowellLeagh Powell New York, NY More articles by this author , Ming Ming LeeMing Ming Lee New York, NY More articles by this author , Douglas ScherrDouglas Scherr New York, NY More articles by this author , Lorraine GudasLorraine Gudas New York, NY More articles by this author , and Nigel MonganNigel Mongan New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.990AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A role for estrogen receptor (ER) signaling in transitional cell carcinoma (TCC) of the bladder has been suggested based on clinical reports of more advanced disease in female patients compared to males. ER-beta is the predominant receptor isoform in bladder TCC while ER-alpha expression is rare. Here we test whether ER-beta levels in bladder TCC patients correlates with clinicopathologic predictors of aggressive disease and whether pharmacologic targeting of this receptor has growth inhibitory properties in vitro. METHODS Immunohistochemistry using a monoclonal antibody to ER-beta was performed in 72 radical cystectomy patient specimens, resulting in evaluation of 129 tissue samples (59 cancer, 70 benign). ER-beta tissue levels were tested for association with 16 clinicopathologic variables in addition to patient survival outcomes. ER-beta protein was measured in 5 cell lines established from bladder cancer patients, and effects on cell growth were determined following treatment with estradiol or ER-beta-selective agonist diarylpropionitrile (DPN) in the presence or absence of tamoxifen. RESULTS ER-beta levels were significantly higher in TCC specimens compared to benign urothelium (p<0.001). While levels of ER-beta did not correlate with bladder tumor stage, expression was strongly associated with aggressive tumor histology, including lymphovascular invasion (p=0.001) and perineural invasion (p=0.004). ER-beta tissue levels were significantly higher in patients with prior pelvic irradiation (p=0.034). Higher bladder levels of ER-beta significantly predicted recurrence (p=0.044) and cancer-specific survival (p=0.027) following radical cystectomy. (FIGURE) All bladder cancer cell lines expressed ER-beta, and treatment with estradiol or DPN led to a significant increase in proliferation in vitro, an effect partially or completely reversed by coadministration of tamoxifen. CONCLUSIONS This study supports a role for ER-beta in bladder carcinogenesis and as a potential prognostic biomarker predicting aggressive histology and poor patient outcomes following radical cystectomy. Further study is warranted to determine whether pharmacologic targeting of ER-beta provides an effective therapeutic strategy in bladder cancer patients. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e364 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Metrics Author Information Eric Kauffman Bethesda, MD More articles by this author Brian Robinson New York, NY More articles by this author Martin Downes Dublin, Ireland More articles by this author Katarzyna Marcinkiewicz New York, NY More articles by this author Leagh Powell New York, NY More articles by this author Ming Ming Lee New York, NY More articles by this author Douglas Scherr New York, NY More articles by this author Lorraine Gudas New York, NY More articles by this author Nigel Mongan New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...