Udager AM, Pan J, Magers MJ,et al.Molecular and Immunohistochemical Characterization Reveals Novel BRAF Mutations in Metanephric Adenoma. Am J Surg Pathol. 2015 ,[Epub ahead of print]
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.
后肾腺瘤（MA）是由原始的后肾肾小管细胞肿瘤性增生组成的一种罕见的良性肾脏肿瘤。目前研究已经证实约90%的MA存在BRAF V600E突变，并且发现BRAF基因15号外显子突变在肾细胞癌和嗜酸细胞瘤中极其罕见。最近在对一组小样本MA的随访研究中，已经通过免疫组化（IHC）检测到了BRAF V600E突变。作者在一组大样本、独立组的MA研究中发现BRAF V600E IHC的敏感性达88%，而特异性高达100%。另外，在2例MA中发现存在新的BRAF基因15号外显子突变，包括V600D错义突变及混合V600D 和K601L错义突变。同时作者通过组织芯片技术评估了BRAF V600E IHC在一些常见肾肿瘤中的表达，结果发现不同肾细胞癌亚型中均无显著的表达。以上数据表明BRAF V600E IHC在诊断MA中有着极其重要的作用，BRAF基因15号外显子突变谱系的扩大，是MA罕见且特有的。