Histopathology 2015, 67, 562–567. DOI: 10.1111/his.12674

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BRAF V600E mutational status in bile duct adenomas and hamartomas Ana€ıs Pujals,1,2,3 Paulette Bioulac-Sage,4,5 Claire Castain,4,5 Cecile Charpy,1 Elie Serge Zafrani1,2 & Julien Calderaro1,2,6 1

Department of Pathology, Assistance Publique-H^opitaux de Paris, CHU Henri Mondor, Creteil, France, 2Faculte de Medecine, Universite Paris-Est Creteil, Creteil, France, 3Inserm U955, Equipe 9, Institut Mondor de Recherche Biomedicale, Creteil, France, 4Department of Pathology, CHU de Bordeaux, Pellegrin Hospital, Bordeaux, France, 5 Inserm, UMR-1053, Universite de Bordeaux, Bordeaux, France, and 6Inserm U955 Equipe 18, Institut Mondor de Recherche Biomedicale, Creteil, France Date of submission 1 October 2014 Accepted for publication 13 February 2015 Published online Article Accepted 19 February 2015

Pujals A, Bioulac-Sage P, Castain C, Charpy C, Zafrani E S & Calderaro J (2015) Histopathology 67, 562–567. DOI:10.1111/his.12674

BRAF V600E mutational status in bile duct adenomas and hamartomas 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.

Keywords: bile duct adenoma, bile duct hamartoma, BRAF, cholangiocarcinoma, V600E

Introduction Bile duct hamartomas (BDH) and bile duct adenomas (BDA) are benign bile duct lesions of unknown pathogenesis.

Address for correspondence: J Calderaro, Departement de Pathologie, H^ opital Henri Mondor, 51 avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France. e-mail: [email protected] © 2015 John Wiley & Sons Ltd.

Most often identified during surgical procedures, BDH, also called von Meyenburg complexes, usually present as multiple and small (

BRAF V600E mutational status in bile duct adenomas and hamartomas.

Bile duct adenomas (BDA) and bile duct hamartomas (BDH) are benign bile duct lesions considered neoplastic or secondary to ductal plate malformation, ...
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