Anaïs Pujals1,2,3, Paulette Bioulac-Sage4,5, Claire Castain4,5, Cécile Charpy1, Elie Serge Zafrani1,2, Julien Calderaro1,2,6. 1. Department of Pathology, Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor, Créteil, France. 2. Faculté de Médecine, Université Paris-Est Créteil, Créteil, France. 3. Inserm U955, Equipe 9, Institut Mondor de Recherche Biomédicale, Créteil, France. 4. Department of Pathology, CHU de Bordeaux, Pellegrin Hospital, Bordeaux, France. 5. Inserm, UMR-1053, Université de Bordeaux, Bordeaux, France. 6. Inserm U955 Equipe 18, Institut Mondor de Recherche Biomédicale, Créteil, France.
Abstract
AIMS: Bile duct adenomas (BDA) and bile duct hamartomas (BDH) are benign bile duct lesions considered neoplastic or secondary to ductal plate malformation, respectively. We have reported previously a high prevalence of BRAF V600E mutations detected by allele-specific polymerase chain reaction assay in BDA, and suggested that BDA may be precursors to a subset of intrahepatic cholangiocarcinomas harbouring V600E mutations. The aim of the present study was to assess the existence of BRAF V600E mutations, using immunohistochemical methods, in additional BDA as well as in BDH. METHODS AND RESULTS: Fifteen BDA and 35 BDH were retrieved from the archives of the pathology departments of two French university hospitals. All cases were reviewed by two pathologists specialized in liver diseases. BRAF V600E mutational status was investigated by immunohistochemistry. Mutated BRAF mutant protein was detected in 53% of the BDA and in none of the cases of BDH. CONCLUSION: Our findings suggest that BDA and BDH are different processes, and that BDA represent true benign neoplasms. They also support the hypothesis that mutated BDA might precede the development of the subset of intrahepatic cholangiocarcinomas harbouring BRAF V600E mutations.
AIMS: Bile duct adenomas (BDA) and bile duct hamartomas (BDH) are benign bile duct lesions considered neoplastic or secondary to ductal plate malformation, respectively. We have reported previously a high prevalence of BRAFV600E mutations detected by allele-specific polymerase chain reaction assay in BDA, and suggested that BDA may be precursors to a subset of intrahepatic cholangiocarcinomas harbouring V600E mutations. The aim of the present study was to assess the existence of BRAFV600E mutations, using immunohistochemical methods, in additional BDA as well as in BDH. METHODS AND RESULTS: Fifteen BDA and 35 BDH were retrieved from the archives of the pathology departments of two French university hospitals. All cases were reviewed by two pathologists specialized in liver diseases. BRAFV600E mutational status was investigated by immunohistochemistry. Mutated BRAF mutant protein was detected in 53% of the BDA and in none of the cases of BDH. CONCLUSION: Our findings suggest that BDA and BDH are different processes, and that BDA represent true benign neoplasms. They also support the hypothesis that mutated BDA might precede the development of the subset of intrahepatic cholangiocarcinomas harbouring BRAFV600E mutations.
Authors: Kwun Wah Wen; Peter S Rabinovitch; Dongliang Wang; Aras N Mattis; Linda D Ferrell; Won-Tak Choi Journal: Virchows Arch Date: 2020-04-15 Impact factor: 4.064