MP47-20 IDENTIFICATION OF ACTIONABLE TARGETS IN CHROMOPHOBE RENAL CELL CARCINOMA DETECTED BY MULTIPLATFORM MOLECULAR ANALYSIS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2015MP47-20 IDENTIFICATION OF ACTIONABLE TARGETS IN CHROMOPHOBE RENAL CELL CARCINOMA DETECTED BY MULTIPLATFORM MOLECULAR ANALYSIS Philip Abbosh, Sherri Millis, Nancy Doll, Adam Hauben, Sandeep Reddy, Daniel Geynisman, and Robert Uzzo Philip AbboshPhilip Abbosh More articles by this author , Sherri MillisSherri Millis More articles by this author , Nancy DollNancy Doll More articles by this author , Adam HaubenAdam Hauben More articles by this author , Sandeep ReddySandeep Reddy More articles by this author , Daniel GeynismanDaniel Geynisman More articles by this author , and Robert UzzoRobert Uzzo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1540AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Chromophobe renal cell carcinoma (chRCC) is a rare kidney cancer subtype that infrequently metastasizes or recurs after definitive local therapy. Limited biomarker data exists to prognosticate outcome or predict response to therapy. We explored the utility of a CLIA-certified biomarker panel which uses immunohistochemistry (IHC) and targeted next generation sequencing (tNGS) to assess presence of druggable targets with the intent of developing targeted therapy protocols in patients with (chRCC). Because of the non-aggressive nature of small chRCCs, we excluded T1a tumors. METHODS Cases were identified from 65,000+ tumors submitted for commercial testing at Caris Life Sciences. All tissues were internally reviewed by a dedicated genitourinary pathologist to confirm diagnosis. Markers were analyzed on tumor tissue removed during partial or radical nephrectomy. IHC was performed on 19 proteins. FISH was performed on EGFR, HER2, and TOP2A. tNGS was performed on 47 genes. RESULTS Twelve patients with chRCC underwent biomarker panel testing. Five patients had metastatic disease. Median age was 54 years old; 50% of patients were male. One patient had a T1b tumor, two patients had T2 tumors, 8 patients had T3 tumors, and one had a T4 tumor. Thymidylate synthase (TS), ribonucleotide reductase M1 (RRM1), and O-6-methylguanine-DNA methyltransferase (MGMT) expression was absent in 12/12, 11/12 and 11/12 tumors, respectively. PTEN expression was absent in 7/12 of tumors. cKIT and PDGFR was expressed in 6/9 and 0/4 tumors, respectively. Lastly, point mutations in APC and TP53 were detected in 1/7 and 3/7 tumors, respectively. No mutations were identified in the other 45 genes tested and no changes in copy number were identified. CONCLUSIONS Biomarker analysis showed that advanced chRCC might be amenable to chemotherapy with 5-fluorouracil, gemcitabine, or temozolamide because of absent TS, RRM1, and MGMT expression, respectively. Such rationale has been used successfully in targeted treatment of other cancers. In addition, sunitinib or imatinib but not sorafenib might be preferred tyrosine kinase inhibitors, as cKIT but not PDGFR was detected. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e559 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Philip Abbosh More articles by this author Sherri Millis More articles by this author Nancy Doll More articles by this author Adam Hauben More articles by this author Sandeep Reddy More articles by this author Daniel Geynisman More articles by this author Robert Uzzo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...