PMID- 28840857 OWN - NLM STAT- MEDLINE DCOM- 20190107 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Linking) VI - 31 IP - 1 DP - 2018 Jan TI - Detection of 6 TFEB-amplified renal cell carcinomas and 25 renal cell carcinomas with MITF translocations: systematic morphologic analysis of 85 cases evaluated by clinical TFE3 and TFEB FISH assays. PG - 179-197 LID - 10.1038/modpathol.2017.99 [doi] AB - Renal cell carcinomas with MITF aberrations demonstrate a wide morphologic spectrum, highlighting the need to consider these entities within the differential diagnosis of renal tumors encountered in clinical practice. Herein, we describe our experience with application of clinical fluorescence in situ hybridization (FISH) assays for detection of TFE3 and TFEB gene aberrations from 85 consecutive renal cell carcinoma cases submitted to our genitourinary FISH service. Results from 170 FISH assays performed on these tumors were correlated with available clinicopathologic findings. Ninety-eight percent of renal tumors submitted for FISH evaluation were from adult patients. Thirty-one (37%) tumors were confirmed to demonstrate MITF aberrations (21 TFE3 translocation, 4 TFEB translocation, and 6 TFEB amplification cases). Overall, renal cell carcinomas with MITF aberrations demonstrated morphologic features overlapping with clear cell, papillary, or clear cell papillary renal cell carcinomas. Renal cell carcinomas with MITF aberrations were significantly more likely to demonstrate dual (eosinophilic and clear) cytoplasmic tones (P=0.030), biphasic TFEB translocation renal cell carcinoma-like morphology (P=0.002), psammomatous calcifications (P=0.002), and nuclear pseudoinclusions (P=0.001) than renal cell carcinomas without MITF aberrations. Notably, 7/9 (78%) renal cell carcinomas exhibiting subnuclear clearing and linear nuclear array (6 of which showed high World Health Organization/International Society of Urological Pathology nucleolar grade) demonstrated TFE3 translocation, an association that was statistically significant when compared with renal cell carcinomas without MITF aberrations (P=0.009). In this cohort comprising consecutive cases, TFEB-amplified renal cell carcinomas were more commonly identified than renal cell carcinomas with TFEB translocations, and four (67%) of these previously unreported TFEB-amplified renal cell carcinomas demonstrated oncocytic and papillary features with a high World Health Organization/International Society of Urological Pathology nucleolar grade. In summary, TFE3 and TFEB FISH evaluation aids in identification and accurate classification of renal cell carcinomas with MITF aberrations, including TFEB-amplified renal cell carcinoma, which may demonstrate aggressive behavior. FAU - Skala, Stephanie L AU - Skala SL AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. FAU - Xiao, Hong AU - Xiao H AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. AD - Clinical Cytogenetics Laboratory, University of Michigan Health System, Ann Arbor, MI,USA. FAU - Udager, Aaron M AU - Udager AM AUID- ORCID: 0000-0002-8254-5404 AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. FAU - Dhanasekaran, Saravana M AU - Dhanasekaran SM AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. FAU - Shukla, Sudhanshu AU - Shukla S AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. FAU - Zhang, Yang AU - Zhang Y AD - Clinical Cytogenetics Laboratory, University of Michigan Health System, Ann Arbor, MI,USA. FAU - Landau, Carrie AU - Landau C AD - Clinical Cytogenetics Laboratory, University of Michigan Health System, Ann Arbor, MI,USA. FAU - Shao, Lina AU - Shao L AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. AD - Clinical Cytogenetics Laboratory, University of Michigan Health System, Ann Arbor, MI,USA. FAU - Roulston, Diane AU - Roulston D AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. AD - Clinical Cytogenetics Laboratory, University of Michigan Health System, Ann Arbor, MI,USA. FAU - Wang, Lisha AU - Wang L AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. FAU - Siddiqui, Javed AU - Siddiqui J AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. FAU - Cao, Xuhong AU - Cao X AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. FAU - Magi-Galluzzi, Cristina AU - Magi-Galluzzi C AD - Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Zhang, Miao AU - Zhang M AD - University of Texas-MD Anderson Cancer Center, Houston, TX, USA. FAU - Osunkoya, Adeboye O AU - Osunkoya AO AD - Departments of Pathology and Urology, Emory University School of Medicine, Atlanta, GA, USA. FAU - Smith, Steven C AU - Smith SC AUID- ORCID: 0000-0003-0982-4607 AD - Virginia Commonwealth University School of Medicine, Richmond, VA, USA. FAU - McKenney, Jesse K AU - McKenney JK AD - Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Betz, Bryan L AU - Betz BL AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. FAU - Myers, Jeffrey L AU - Myers JL AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. FAU - Chinnaiyan, Arul M AU - Chinnaiyan AM AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. AD - Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA. AD - Howard Hughes Medical Institute, Ann Arbor, MI, USA. FAU - Tomlins, Scott A AU - Tomlins SA AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. AD - Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA. FAU - Mehra, Rohit AU - Mehra R AD - Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. AD - Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA. LA - eng GR - HHMI/Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170825 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) RN - 0 (Biomarkers, Tumor) RN - 0 (MITF protein, human) RN - 0 (Microphthalmia-Associated Transcription Factor) RN - 0 (TFE3 protein, human) RN - 0 (TFEB protein, human) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics MH - Biomarkers, Tumor/analysis/genetics MH - Carcinoma, Renal Cell/*genetics MH - Child MH - Female MH - Gene Amplification MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - Kidney Neoplasms/*genetics MH - Male MH - Microphthalmia-Associated Transcription Factor/genetics MH - Middle Aged MH - Translocation, Genetic MH - Young Adult EDAT- 2017/08/26 06:00 MHDA- 2019/01/08 06:00 CRDT- 2017/08/26 06:00 PHST- 2017/05/01 00:00 [received] PHST- 2017/06/16 00:00 [revised] PHST- 2017/06/29 00:00 [accepted] PHST- 2017/08/26 06:00 [pubmed] PHST- 2019/01/08 06:00 [medline] PHST- 2017/08/26 06:00 [entrez] AID - S0893-3952(22)01733-1 [pii] AID - 10.1038/modpathol.2017.99 [doi] PST - ppublish SO - Mod Pathol. 2018 Jan;31(1):179-197. doi: 10.1038/modpathol.2017.99. Epub 2017 Aug 25.