MP08-07 GENOMIC PROFILING OF CT1A CLEAR CELL RENAL CELL CARCINOMA FOR PREDICTING AGGRESSIVE PATHOLOGY

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP08)1 Apr 2020MP08-07 GENOMIC PROFILING OF CT1A CLEAR CELL RENAL CELL CARCINOMA FOR PREDICTING AGGRESSIVE PATHOLOGY Zeyad Schwen*, Hiten Patel, Michael Biles, Joseph Cheaib, Ridwan Alam, Michael Gorin, Michael Johnson, Mohamad Allaf, Alexander Baras, and Phillip Pierorazio Zeyad Schwen*Zeyad Schwen* More articles by this author , Hiten PatelHiten Patel More articles by this author , Michael BilesMichael Biles More articles by this author , Joseph CheaibJoseph Cheaib More articles by this author , Ridwan AlamRidwan Alam More articles by this author , Michael GorinMichael Gorin More articles by this author , Michael JohnsonMichael Johnson More articles by this author , Mohamad AllafMohamad Allaf More articles by this author , Alexander BarasAlexander Baras More articles by this author , and Phillip PierorazioPhillip Pierorazio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000828.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A greater emphasis has been placed on illuminating the mutational landscape of renal cell carcinoma (RCC) to better understanding the underlying tumor biology to predict tumor aggressiveness. While much of the focus has been on advanced and metastatic RCC, we aimed at identifying whether somatic mutations are also prognostic for aggressive pathology in the small renal mass for better patient selection for active surveillance or surgical treatment. METHODS: From an IRB-approved institutional tissue biorepository, surgically removed cT1a (<4cm) clear cell RCC (ccRCC) specimens were selected. Those with any nodal or metastatic disease as well as hereditary or genetic RCC syndromes were excluded. DNA was isolated from formalin-fixed paraffin-embedded tissue and sent for targeted sequencing using an 8-gene panel including VHL, SETD2, PBRM1, KDM5c, BAP1, PTEN, and TP53. Mutational type and frequencies were recorded for each specimen and were evaluated for associations with high tumor grade (ISUP 3, 4) and upstaging to pT3a. RESULTS: 70 consecutive tissue samples from cT1a renal masses were isolated for analysis. Patients were mostly male (61.3%) and more frequently underwent a partial nephrectomy (82.3%). Median tumor size was 2.5cm (IQR 1.9-3.3cm). 88.6% (62/70) of tumors had at least one mutation with VHL (39/70, 55.7%) and SETD2 (55/70, 78.6%) as the most frequent mutations (Table 1). Notably, we found BAP1 mutations to be significant associated with high grade (ISUP 3 or 4) or upstaging to pT3a (p < 0.036) and PBRM1 was significantly associated with upstaging (p < 0.047) (Figure 1). Also, BAP1 and KDM5c had a high PPV for high grade or upstaging (71% and 75%, respectively). The number of mutations and type of mutation were not found to be associated with upstaging or high grade pathology. CONCLUSIONS: Somatic mutations are common in cT1a ccRCC tumors and BAP1 and PBRM1 mutations were found to be associated with higher tumor grade and upstaging to pT3a which may be useful for better selecting patients for active surveillance. Larger, prospective studies are required. Source of Funding: National Kidney Foundation of Maryland © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e107-e108 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zeyad Schwen* More articles by this author Hiten Patel More articles by this author Michael Biles More articles by this author Joseph Cheaib More articles by this author Ridwan Alam More articles by this author Michael Gorin More articles by this author Michael Johnson More articles by this author Mohamad Allaf More articles by this author Alexander Baras More articles by this author Phillip Pierorazio More articles by this author Expand All Advertisement PDF downloadLoading ...