Molecular and Immunohistochemical Characterization Reveals Novel BRAF Mutations in Metanephric Adenoma. (April 2015)

• Record Type: Journal Article
• Authors: Udager, Aaron M.; Pan, Jincheng; Magers, Martin J.; Palapattu, Ganesh S.; Morgan, Todd M.; Montgomery, Jeffrey S.; Weizer, Alon Z.; Hafez, Khaled S.; Miller, David C.; Wolf, James S.; McHugh, Jonathan B.; Chinnaiyan, Arul M.; Dhanasekaran, Saravana M.; Mehra, Rohit
• Is Part Of: American journal of surgical pathology. Volume 39:Number 4(2015)
• Publication Date: 2015-04
• Subjects: BRAF -- metanephric adenoma -- immunohistochemistry -- V600E -- Sanger sequencing; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000000377
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : Metanephric adenoma (MA) is a rare benign renal tumor comprised of a neoplastic proliferation of primitive metanephric tubular cells. A previous study identified BRAF V600E mutations in approximately 90% of MA and found that similar BRAF exon 15 mutations are exceedingly rare in other common renal tumors, including renal cell carcinoma and oncocytoma. A recent follow-up study has validated mutation-specific immunohistochemistry (IHC) for detection of BRAF V600E mutations in a small cohort of MA. Here, we extend these findings to a larger, independent cohort of MA, demonstrating an overall 88% sensitivity and 100% specificity for BRAF V600E IHC. In addition, we report 2 cases of MA with novel BRAF exon 15 mutations, including a V600D missense mutation and a compound V600D and K601L missense mutation. Finally, we evaluate BRAF V600E IHC in a large tissue microarray cohort of common renal tumors and find no significant expression in several renal cell carcinoma subtypes. These data support a role for BRAF V600E IHC in diagnostically challenging cases of MA and expand the spectrum of BRAF exon 15 mutations in this uncommon but unique renal neoplasm.