Research Papers:

Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation

Anna Caliò, John N. Eble, Ondrej Hes, Guido Martignoni, Saul E. Harari, Sean R. Williamson, Matteo Brunelli, Adeboye O. Osunkoya, Lisha Wang, Eva Comperat, Antonio Lopez-Beltran, Mingsheng Wang, Shaobo Zhang, Kendra L. Curless, Kristin M. Post, Hsim-Yee Chang, Claudio Luchini, Lee Ann Baldrige, Gregory T. MacLennan, Rodolfo Montironi, David J. Grignon and Liang Cheng _

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Oncotarget. 2017; 8:54096-54105. https://doi.org/10.18632/oncotarget.11117

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Anna Caliò1,2, John N. Eble1, Ondrej Hes3, Guido Martignoni2,4, Saul E. Harari1, Sean R. Williamson5, Matteo Brunelli2, Adeboye O. Osunkoya6, Lisha Wang7, Eva Comperat8, Antonio Lopez-Beltran9, Mingsheng Wang1, Shaobo Zhang1, Kendra L. Curless1, Kristin M. Post1, Hsim-Yee Chang1, Claudio Luchini1,2, Lee Ann Baldrige1, Gregory T. MacLennan10, Rodolfo Montironi11, David J. Grignon1 and Liang Cheng1

1Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

2Department of Pathology, University of Verona, Verona, Italy

3Department of Pathology, Charles University Hospital Plzeň, Pilsen, Czech Republic

4Department of Pathology, Pederzoli Hospital, Peschiera, Italy

5Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, Michigan, USA

6Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA

7Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA

8Department of Pathology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

9Unit of Anatomical Pathology, Department of Surgery, Faculty of Medicine, Cordoba, Spain and Champalimaud Clinical Center, Lisbon, Portugal

10Departments of Pathology and Laboratory Medicine, Case Western Reserve University, Cleveland, Ohio, USA

11Department of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of The Marche Region (Ancona), Ancona, Italy

Correspondence to:

Liang Cheng, email: [email protected]

Keywords: kidney, metanephric adenoma, BRAF, nephroblastoma/Wilms tumor, immunohistochemistry

Received: March 08, 2016      Accepted: July 07, 2016      Published: August 08, 2016


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.

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