MP65-16 NOVEL BIOMARKER SIGNATURE FOR PREDICTING PATHOLOGIC RESPONSE OF UROTHELIAL CARCINOMA OF THE BLADDER TO CISPLATIN-BASED NEOADJUVANT CHEMOTHERAPY

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III1 Apr 2018MP65-16 NOVEL BIOMARKER SIGNATURE FOR PREDICTING PATHOLOGIC RESPONSE OF UROTHELIAL CARCINOMA OF THE BLADDER TO CISPLATIN-BASED NEOADJUVANT CHEMOTHERAPY Patrick Hensley, Matthew Purdom, Natasha Kyprianou, Chi Wang, and Andrew James Patrick HensleyPatrick Hensley More articles by this author , Matthew PurdomMatthew Purdom More articles by this author , Natasha KyprianouNatasha Kyprianou More articles by this author , Chi WangChi Wang More articles by this author , and Andrew JamesAndrew James More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2082AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cisplatin-based neoadjuvant chemotherapy (NC) has become standard practice in the management of muscle invasive urothelial carcinoma of the bladder, but it confers only a modest survival advantage. Patients with pathologic progression on NC have poor outcomes and may benefit from upfront cystectomy. We previously demonstrated that phenotypic epithelial-mesenchymal transition (EMT) is associated with advanced stage and grade. This study pursued the predictive value of EMT signature effectors of bladder cancer therapeutic response to NC. METHODS A tissue microarray (TMA) was constructed with matched pre-NC transurethral resection (TUR) specimens and post-NC cystectomy specimens from the same patients (N=69) with specimens from patients managed with surgery alone serving as control (N=21). TMA sections were immunostained for the EMT biomarkers E-cadherin (epithelial marker), N-cadherin and Vimentin (mesenchymal markers) and β-catenin (EMT effector) and staining intensity was scored by two blinded reviewers. Data was statistically analyzed using 1-way ANOVA and T-tests. RESULTS Increased expression of the mesenchymal markers Vimentin and N-cadherin on TUR specimen was associated with nodal metastasis and extravesical disease (≥ypT3 or N+) at the time of cystectomy (P=0.019 and 0.002, respectively). Decreased Vimentin and N-cadherin expression independently predicted complete pathologic response to NC (ypT0, P<0.001 and 0.024, respectively). In post-NC cystectomy specimens, only N-cadherin expression was correlated with pathologic stage (P=0.004). In TUR specimens from patients managed with surgery alone, increased expression of β-catenin and N-cadherin predicted extravesical disease at the time of cystectomy (P=0.033 and 0.007, respectively). When comparing pre- and post-NC specimens, treatment with platinum-based NC induced a mixed EMT picture, with stable β-catenin and N-cadherin expression and decreased E-cadherin and Vimentin expression, relative to control patients. Expression patterns in metastatic lymph node tissue was inconsistent. CONCLUSIONS Expression of EMT markers have potential value in predicting pathologic response to cisplatin-based NC. Further validation is necessary to correlate these findings with clinical outcomes and establish these as novel biomarkers of adverse response to NC towards the goal of optimizing patient selection for NC. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e864-e865 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Patrick Hensley More articles by this author Matthew Purdom More articles by this author Natasha Kyprianou More articles by this author Chi Wang More articles by this author Andrew James More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...