MP29-06 IQGAP1 EXPRESSION AND SURVIVAL IN CLEAR CELL RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2014MP29-06 IQGAP1 EXPRESSION AND SURVIVAL IN CLEAR CELL RENAL CELL CARCINOMA Philip Barbosa, Olfat Hammam, Rosalie Nolley, Thomas Metzner, Alice Fan, Sandy Srinivas, Donna Peehl, James Brooks, and John Leppert Philip BarbosaPhilip Barbosa More articles by this author , Olfat HammamOlfat Hammam More articles by this author , Rosalie NolleyRosalie Nolley More articles by this author , Thomas MetznerThomas Metzner More articles by this author , Alice FanAlice Fan More articles by this author , Sandy SrinivasSandy Srinivas More articles by this author , Donna PeehlDonna Peehl More articles by this author , James BrooksJames Brooks More articles by this author , and John LeppertJohn Leppert More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.748AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a scaffold protein that is over-expressed in many tumors dependent on receptor tyrosine kinase/RAS/RAF signaling. Blocking IQGAP1 can disrupt oncogenic signaling and may offer a novel therapeutic approach in Renal Cell Carcinoma (RCC). We sought to characterize the expression of IQGAP1 in RCC. METHODS First, we evaluated IQGAP1 expression in a tissue microarray of normal renal parenchyma. Next, we scored IQGAP1 expression in a TMA of RCC (N=297), including clear cell (N=213), papillary (N=21), chromophobe (N=20), unclassified RCC (N=29), and oncocytoma (N=14). Nuclear and cytoplasmic staining intensity (0 to 3+), and the percentage of tumor cells expressing the marker was scored. Staining was correlated with tumor factors (histology, grade, size, the presence of regional or distant metastasis). We created logistic regression models to test the association of IQGAP1 expression with the presence of metastasis at diagnosis or disease recurrence. Unadjusted overall survival and recurrence free survival was visualized using the Kaplan-Meier method. RESULTS IQGAP1 expression was identified in 96% of RCC tumors and demonstrated distinct staining patterns. Cytoplasmic staining was strongest among papillary (67% mean positivity, intensity 2.3) and chromophobe RCC (100% positivity, intensity 2.2). Nuclear expression was identified in 53% of clear cell RCC with a mean intensity of 1.3 (Fig 1). Papillary RCC demonstrated modest nuclear expression in 29% of tumors with a mean intensity of 0.7. Among clear cell RCC, nuclear expression of IQGAP was associated with overall and recurrence free survival (p=0.011) (Fig 2). Conversely higher cytoplasmic expression was associated with mortality (p=0.016). CONCLUSIONS IQGAP1 holds promise as a novel prognostic biomarker and therapeutic target in clear cell RCC. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e306-e307 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Philip Barbosa More articles by this author Olfat Hammam More articles by this author Rosalie Nolley More articles by this author Thomas Metzner More articles by this author Alice Fan More articles by this author Sandy Srinivas More articles by this author Donna Peehl More articles by this author James Brooks More articles by this author John Leppert More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...