title: Molecular and immunohistochemical characterization reveals novel BRAF mutations in metanephric adenoma.
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.
authors.affiliation: Departments of *Pathology ‡Urology §Comprehensive Cancer Center, University of Michigan Health System ∥Michigan Center for Translational Pathology ¶Howard Hughes Medical Institute, Ann Arbor, MI †Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Udager
authors.forename: Jincheng
authors.initials: J
authors.lastname: Pan
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Magers
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Palapattu
authors.forename: Todd M
authors.initials: TM
authors.lastname: Morgan
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Montgomery
authors.forename: Alon Z
authors.initials: AZ
authors.lastname: Weizer
authors.forename: Khaled S
authors.initials: KS
authors.lastname: Hafez
authors.forename: David C
authors.initials: DC
authors.lastname: Miller
authors.forename: James S
authors.initials: JS
authors.lastname: Wolf
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf