Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation.

Anna Caliò,Rodolfo Montironi,Lisha Wang,Matteo Brunelli,Shaobo Zhang,Mingsheng Wang,Gregory T Maclennan,Claudio Luchini,John N Eble,Guido Martignoni,Sean R Williamson,Lee Ann Baldrige,Adeboye O Osunkoya,David J Grignon,Kristin Post ,Ondřej Hes ,Hsim Y Chang ,Saul Harari ,Antonio López-Beltrán ,Kendra Curless ,Éva Compérat ,Cheng Liu

doi:10.18632/oncotarget.11117

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.

Highlights

Metanephric adenoma of the kidney is an uncommon benign neoplasm which is usually asymptomatic and discovered incidentally
It is worth noting that clinical trials have recently emerged proposing targeted therapy for nonmelanoma cancers harboring BRAF mutations, demonstrating the important role of BRAFtesting [33]
Attention to the association of BRAF mutation with metanephric adenoma has been drawn by a few case reports and small series [7, 8, 10, 11, 34]

Summary

Introduction

Metanephric adenoma of the kidney is an uncommon benign neoplasm which is usually asymptomatic and discovered incidentally. These tumors mostly occur in middle-aged individuals, with a female predominance (2:1), the age distribution is broad, ranging from children to the elderly [1,2,3,4]. Metanephric adenomas are typically circumscribed, not-encapsulated, solid masses. These neoplasms are typically composed of small epithelial cells arranged as tightly packed small acini. Metanephric adenoma lacks the gains of chromosome 7 and 17 and losses of Y that are typical of papillary renal cell carcinoma [6]

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Results

Conclusion