Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation

Abstract

<i>BRAF</i> mutation recently has been reported in metanephric adenoma. We sought to determine the clinical and morphologic features of <i>BRAF</i>-mutated metanephric adenoma and to correlate <i>BRAF</i> mutation with BRAF V600E immunohistochemical staining results. A series of 48 metanephric adenomas and 15 epithelial-predominant nephroblastomas were analyzed for the occurrence of <i>BRAF</i> mutation (<i>BRAF</i> V600E/V600E complex, <i>BRAF</i> V600D, <i>BRAF</i> V600K and <i>BRAF</i> 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 <i>BRAF</i> V600E mutation; none of the other <i>BRAF</i> variants was detected. Of 41 <i>BRAF</i>-mutated metanephric adenomas, 33 showed positive VE1 immunostaining (sensitivity 80%, specificity 100%); in all cases we detected p16^INK4 expression regardless of <i>BRAF</i> mutation status. All epithelial-predominant nephroblastomas were <i>BRAF</i>-wild-type and none expressed VE1. The following features were associated with <i>BRAF</i> 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, <i>BRAF</i>-mutated metanephric adenomas were associated with older age, female predominance, and the presence of a predominant acinar component. A subset (20%) of <i>BRAF</i>-mutated metanephric adenomas was not detected by VE1 immunostaining.