Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation

• Type of Material: Article
• Authors: Anna Caliò, Indiana University School of Medicine; John N. Eble, Indiana University School of Medicine; Ondrej Hes, Charles University Hospital Plzeň; Guido Martignoni, University of Verona; Saul E. Harari, Indiana University School of Medicine; Sean R. Williamson, Henry Ford Health System; Matteo Brunelli, University of Verona; Adeboye Osunkoya, Emory University; Lisha Wang, University of Michigan; Eva Comperat, Groupe Hospitalier Pitié-Salpêtrière; Antonio Lopez-Beltran, Champalimaud Clinical Center; Mingsheng Wang, Indiana University School of Medicine; Shaobo Zhang, Indiana University School of Medicine; Kendra L. Curless, Indiana University School of Medicine; Kristin M. Post, Indiana University School of Medicine; Hsim-Yee Chang, Indiana University School of Medicine; Claudio Luchini, Indiana University School of Medicine; Lee Ann Baldrige, Indiana University School of Medicine; Gregory T. MacLennan, Case Western Reserve University; Rodolfo Montironi, Polytechnic University of The Marche Region (Ancona); David J. Grignon, Indiana University School of Medicine; Liang Cheng, Indiana University School of Medicine
• Language: English
• Date: 2016-08-08
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Caliò et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.11117
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 8
• Issue: 33
• Start Page: 54096
• End Page: 54105
• Grant/Funding Information: No funding information available
• Keywords: nephroblastoma/Wilms tumor; immunohistochemistry; metanephric adenoma; kidney; BRAF
• Research Categories: Health Sciences, General; Health Sciences, Pathology

Abstract

BRAF mutation recently has been reported in metanephric adenoma. We sought to determine the clinical and morphologic features of BRAF-mutated metanephric adenoma and to correlate BRAF mutation with BRAF V600E immunohistochemical staining results. A series of 48 metanephric adenomas and 15 epithelial-predominant nephroblastomas were analyzed for the occurrence of BRAF mutation (BRAF V600E/V600E complex, BRAF V600D, BRAF V600K and BRAF V600R) using the BRAF RGQ PCR kit (Qiagen). Immunohistochemistry was performed using monoclonal mouse antibodies against p16INK4 and VE1 (Spring Bioscience), recognizing the BRAF V600E mutant protein. Forty-one of 48 cases (85%) showed BRAF V600E mutation; none of the other BRAF variants was detected. Of 41 BRAF-mutated metanephric adenomas, 33 showed positive VE1 immunostaining (sensitivity 80%, specificity 100%); in all cases we detected p16INK4 expression regardless of BRAF mutation status. All epithelial-predominant nephroblastomas were BRAF-wild-type and none expressed VE1. The following features were associated with BRAF V600E mutation: older patients (p=0.01), female predominance (p=0.005) and the presence of a predominantly acinar architecture (p=0.003). In summary, BRAF-mutated metanephric adenomas were associated with older age, female predominance, and the presence of a predominant acinar component. A subset (20%) of BRAF-mutated metanephric adenomas was not detected by VE1 immunostaining.