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BRAF V600E mutation in biliary proliferations associated with α 1 ‐antitrypsin deficiency
Author(s) -
Angkathunyakul Napat,
Rosini Francesca,
Heaton Nigel,
Foskett Pierre,
Quaglia Alberto
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13083
Subject(s) - mutation , medicine , cancer research , biology , genetics , gene
Aims Both homozygous and heterozygous α 1 ‐antitrypsin (AAT) deficiency patients are at risk of developing hepatocellular carcinoma (HCC), but also of developing cholangiocarcinoma and combined HCC and cholangiocarcinoma. The aim of our study is to report a series of bile duct adenomas (BDAs) and intrahepatic cholangiocarcinoma (ICCs) in adult AAT deficiency patients, observed in our institution over a 5‐year period. Our observational study includes a detailed investigation of their immunohistochemical profile and BRAF V600E mutation status. Methods and results Eleven biliary lesions from five AAT deficiency patients (six BDAs from three cirrhotic patients with other concurrent liver diseases; three BDAs and two ICCs from two non‐cirrhotic patients) were identified between 2010 and 2015 during routine histological investigation. Most BDAs expressed CD56, EpCAM, CD133, and CA19‐9, similarly to hepatic progenitor cells (HPCs), and carried the BRAF V600E mutation (87.5%). One ICC showed a similar immunohistochemical profile but no evidence of the BRAF V600E mutation. Conclusions Most of the biliary proliferations in AAT deficiency patients have an appearance of BDA with an HPC‐related immunohistochemical profile. Their frequent BRAF V600E mutations support their neoplastic nature, but not necessarily their progression to ICC. We believe that this may depend on the patient genotype, or require a different pathway or a second mutational hit for malignant transformation. We postulate that BDA represents a heterogeneous group of biliary lesions, and that those associated with AAT deficiency may constitute a group of their own.