You have accessJournal of UrologyBladder Cancer: Basic Research1 Apr 20111057 PROTEIN ALTERATIONS PREDICT BLADDER CANCER OUTCOME INDEPENDENT OF CLINICOPATHOLOGIC PROGNOSTIC CRITERIA AND TOBACCO SMOKE EXPOSURE Anirban Mitra, Jose Castelao, Debra Hawes, Denice Tsao-Wei, Xuejuan Jiang, Shan Shi, Lillian Young, Ram Datar, Eila Skinner, John Stein, Susan Groshen, Mimi Yu, Ronald Ross, Donald Skinner, Victoria Cortessis, and Richard Cote Anirban MitraAnirban Mitra Los Angeles, CA More articles by this author , Jose CastelaoJose Castelao Los Angeles, CA More articles by this author , Debra HawesDebra Hawes Los Angeles, CA More articles by this author , Denice Tsao-WeiDenice Tsao-Wei Los Angeles, CA More articles by this author , Xuejuan JiangXuejuan Jiang Los Angeles, CA More articles by this author , Shan ShiShan Shi Los Angeles, CA More articles by this author , Lillian YoungLillian Young Los Angeles, CA More articles by this author , Ram DatarRam Datar Miami, FL More articles by this author , Eila SkinnerEila Skinner Los Angeles, CA More articles by this author , John SteinJohn Stein Los Angeles, CA More articles by this author , Susan GroshenSusan Groshen Los Angeles, CA More articles by this author , Mimi YuMimi Yu Minneapolis, MN More articles by this author , Ronald RossRonald Ross Los Angeles, CA More articles by this author , Donald SkinnerDonald Skinner Los Angeles, CA More articles by this author , Victoria CortessisVictoria Cortessis Los Angeles, CA More articles by this author , and Richard CoteRichard Cote Miami, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1094AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer develops through multiple cellular alterations. Traditional molecular profiling studies do not account for cigarette smoking, the most well established risk factor for bladder cancer in the USA, and its influence on outcome. This study examined the prognostic value of molecular alterations across all disease stages after stratifying for clinicopathologic factors and smoking. METHODS 212 patients from the Los Angeles County Cancer Surveillance Program, a NCI/SEER cancer registry were included. To analyze the biologic and molecular impact of smoke exposure, we introduced a novel “smoking intensity” variable that combined a patient's smoking status, duration of smoking and number of cigarettes smoked daily. Primary bladder tumors were immunohistochemically profiled for Bax, caspase-3, Apaf-1, Bcl-2, p53, p21, cyclooxygenase-2, vascular endothelial growth factor, and E-cadherin alterations. Univariate analyses and multivariable modeling were used to examine associations with outcome. RESULTS Median follow up was 13.2 years. The cohort comprised of 78 (37%) noninvasive, 101 (48%) organ-confined, and 33 (15%) advanced bladder tumor patients. 67 (32%), 93 (44%) and 52 (24%) patients were classified as low, intermediate and high smoking intensity candidates, respectively. Increasing pathologic stage and smoking intensity were independently associated with poor survival (p<0.001). p53, E-cadherin, p21 and Apaf-1 expressions were significantly associated with pathologic stage. E-cadherin and p53 were univariately prognostic for outcome (p=0.014 and p=0.032, respectively), and remained predictive after stratifying by smoking intensity. Apaf-1 was the most valuable individual marker, being prognostic univariately (p=0.005), and after stratification by stage (p=0.029), smoking (p=0.03), and both stage and smoking combined (p=0.025). Multivariable modeling confirmed this significance in association. When analyzed in combination, alterations in all nine biomarkers were significantly prognostic for survival by univariate and multivariate stratification. CONCLUSIONS The study confirms detrimental effects of smoking on bladder cancer prognosis. Apaf-1, E-cadherin and p53 can individually predict outcome, with Apaf-1 being the most prognostic individual marker. Increasing biomarker alterations was significantly associated with worsening survival independent of stage and smoking history, although markers comprising the panel were not necessarily prognostic individually. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e425 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anirban Mitra Los Angeles, CA More articles by this author Jose Castelao Los Angeles, CA More articles by this author Debra Hawes Los Angeles, CA More articles by this author Denice Tsao-Wei Los Angeles, CA More articles by this author Xuejuan Jiang Los Angeles, CA More articles by this author Shan Shi Los Angeles, CA More articles by this author Lillian Young Los Angeles, CA More articles by this author Ram Datar Miami, FL More articles by this author Eila Skinner Los Angeles, CA More articles by this author John Stein Los Angeles, CA More articles by this author Susan Groshen Los Angeles, CA More articles by this author Mimi Yu Minneapolis, MN More articles by this author Ronald Ross Los Angeles, CA More articles by this author Donald Skinner Los Angeles, CA More articles by this author Victoria Cortessis Los Angeles, CA More articles by this author Richard Cote Miami, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...