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BRAF V600E mutations in bile duct adenomas

2014; Lippincott Williams & Wilkins; Volume: 61; Issue: 1 Linguagem: Inglês

10.1002/hep.27133

1527-3350

Anaïs Pujals, Giuliana Amaddeo, Claire Castain, Paulette Bioulac‐Sage, Philippe Compagnon, Jessica Zucman‐Rossi, Daniel Azoulay, Karen Leroy, Élie Serge Zafrani, Julien Caldéraro,

Pancreatic and Hepatic Oncology Research

Potential conflict of interest: Nothing to report. To the Editor: Bile duct adenomas (BDA) are rare and benign intrahepatic biliary proliferations of uncertain pathogenesis. They are usually small in size ( 3 3a BDA wt 4 62 M Atypical focal nodular hyperlasia NASH 2 4a BDA V600E 4b BDA wt 5 67 M ICC None 3 5a BDA V600E 5b BDA V600E 5c BDA V600E 5d ICC V600E 6 57 M HCC NASH/Alcohol 1 6a BDA wt 7 76 M ICC None >3 7a BDA wt 7b ICC wt 8 74 M Biliary cyst None 1 8a BDA V600E 9 69 M ICC None 2 9a BDA V600E 9b BDA V600E 9c ICC V600E 10 63 F Pancreatic endocrine tumor None 1 10a BDA wWt Wt, wild‐type; HCC, hepatocellular carcinoma; NASH, nonalcoholic steatohepatitis. BRAF V600E mutations were identified in 8/15 (53%) BDAs (Table 1). The existence of a recurrent molecular alteration such as a BRAF mutation strongly supports the hypothesis that BDAs are true neoplasms and that they should no more be designated as reactive processes or hamartomas. Moreover, V600E mutations were also identified in two out of the four ICC associated with BDA (Table 1). As the BRAF mutation rate in ICC is rather low (5‐10%),5 this observation suggests that BRAF mutated ICC might arise from BDA. BRAF mutations also seem to occur early during carcinogenesis, as observed in the serrated pathway of colon cancer.6 In conclusion, we have identified a high frequency of BRAF V600E mutations in BDAs, suggesting that they are true neoplasms and that they may be important precursors for the subset of ICC exhibiting BRAF mutations. Our findings support an adenoma to carcinoma sequence associated with BRAF mutations in intrahepatic biliary carcinogenesis.