You have accessJournal of UrologyKidney Cancer: Localized II1 Apr 20121297 NUMBER OF ALTERED BIOMARKERS IN THE MAMMALIAN TARGET OF RAPAMYCIN INDEPENDENTLY CORRELATES WITH ONCOLOGIC OUTCOMES IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA Oussama Darwish, Ramy Youssef, Payal Kapur, Aditya Bagrodia, Michael Belsante, Feras Alhalabi, Yair Lotan, and Vitaly Margulis Oussama DarwishOussama Darwish Dallas, TX More articles by this author , Ramy YoussefRamy Youssef Dallas, TX More articles by this author , Payal KapurPayal Kapur Dallas, TX More articles by this author , Aditya BagrodiaAditya Bagrodia Dallas, TX More articles by this author , Michael BelsanteMichael Belsante Dallas, TX More articles by this author , Feras AlhalabiFeras Alhalabi Dallas, TX More articles by this author , Yair LotanYair Lotan Dallas, TX More articles by this author , and Vitaly MargulisVitaly Margulis Dallas, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1631AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Aberrant activation of the mammalian target of rapamycin (mTOR) pathway and hypoxia induced factor (HIF) promotes the invasiveness and metastatic potential in a variety of malignancies. The aim of the present study was to evaluate the association of altered expression of mTOR and HIFpathways components with oncologic outcomes in non-metastatic clear cell renal cell carcinoma (ccRCC). METHODS Immunohistochemistry for p-S6, pmTOR, mTOR, AKT, HIF, RAPTOR, PTEN, PI3K, and p-4E1was performed on tissue microarray constructs of ccRCCs of patients treated with radical or partial nephrectomy between 1997-2010. The relationship between individual altered marker expression, as well as a prognostic marker score (low < 3 altered biomarkers; intermediate 4-5 altered biomarkers; high >5 altered biomarkers) and onocologic outcome was assessed. RESULTS The study included 419 non- metastatic ccRCC patients, 247 males (59%) and 171 females (41%), with mean age 57 years (range, 17-85). Median follow up was 26 months (Range 0-150). The tumors were non-organ confined (pT3-T4) in 86 (20.5%) patients and high grade (3-4) in 131 (31%) patients. The cohort was stratified into low, intermediate and high prognostic marker score found in 214 patients (51%), 152 patients (36%), and 53 patients (13%), respectively. Kaplan Meier survival analysis demonstrated a statistically significant correlation between the different risk groups and disease recurrence (Fig.1). In a multivariate Cox regression analysis, after controlling for tumor stage and grade, high marker score was independent predictor of disease recurrence (HR 3.3 and p = 0.01). CONCLUSIONS The cumulative number of aberrantly expressed biomarkers correlates with aggressive tumor biology and worse oncologic outcomes in patients with ccRCC. Our data supports prospective pathway-based exploration of mTOR signaling cascade to augment current clinico-patholgoic predictors of oncologic outcomes in ccRCC. Oussama Darwish and Ramy Youssef contributed equally. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e525-e526 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Oussama Darwish Dallas, TX More articles by this author Ramy Youssef Dallas, TX More articles by this author Payal Kapur Dallas, TX More articles by this author Aditya Bagrodia Dallas, TX More articles by this author Michael Belsante Dallas, TX More articles by this author Feras Alhalabi Dallas, TX More articles by this author Yair Lotan Dallas, TX More articles by this author Vitaly Margulis Dallas, TX More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...