Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation

// Anna Calio 1, 2 , John N. Eble 1 , Ondrej Hes 3 , Guido Martignoni 2, 4 , Saul E. Harari 1 , Sean R. Williamson 5 , Matteo Brunelli 2 , Adeboye O. Osunkoya 6 , Lisha Wang 7 , Eva Comperat 8 , Antonio Lopez-Beltran 9 , Mingsheng Wang 1 , Shaobo Zhang 1 , Kendra L. Curless 1 , Kristin M. Post 1 , Hsim-Yee Chang 1 , Claudio Luchini 1, 2 , Lee Ann Baldrige 1 , Gregory T. MacLennan 10 , Rodolfo Montironi 11 , David J. Grignon 1 and Liang Cheng 1 1 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA 2 Department of Pathology, University of Verona, Verona, Italy 3 Department of Pathology, Charles University Hospital Plzeň, Pilsen, Czech Republic 4 Department of Pathology, Pederzoli Hospital, Peschiera, Italy 5 Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, Michigan, USA 6 Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA 7 Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA 8 Department of Pathology, Groupe Hospitalier Pitie-Salpetriere, Paris, France 9 Unit of Anatomical Pathology, Department of Surgery, Faculty of Medicine, Cordoba, Spain and Champalimaud Clinical Center, Lisbon, Portugal 10 Departments of Pathology and Laboratory Medicine, Case Western Reserve University, Cleveland, Ohio, USA 11 Department of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of The Marche Region (Ancona), Ancona, Italy Correspondence to: Liang Cheng, email: liang_cheng@yahoo.com Keywords: kidney, metanephric adenoma, BRAF, nephroblastoma/Wilms tumor, immunohistochemistry Received: March 08, 2016 Accepted: July 07, 2016 Published: August 08, 2016 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 p16 INK4 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 p16 INK4 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.