Premium
PBRM1 loss is a late event during the development of cholangiocarcinoma
Author(s) -
Luchini Claudio,
Robertson Scott A,
Hong SeungMo,
Felsenstein Matthäus,
Anders Robert A,
Pea Antonio,
Nottegar Alessia,
Veronese Nicola,
He Jin,
Weiss Matthew J,
Capelli Paola,
Scarpa Aldo,
Argani Pedram,
Kapur Payal,
Wood Laura D
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.13234
Subject(s) - carcinogenesis , intrahepatic cholangiocarcinoma , immunohistochemistry , biology , cancer research , chromatin , tumor suppressor gene , mutation , pathology , gallbladder , somatic cell , gene , medicine , genetics , immunology
Aims Somatic mutations in genes encoding chromatin remodellers have been reported recently in several cancer types, including approximately half of cholangiocarcinomas. One of the most commonly mutated chromatin remodellers in cholangiocarcinoma is the Polybromo‐1 ( PBRM 1 ) gene located on chromosome 3p21, which encodes a subunit of the SWI / SNF complex. The aim of this study was to determine the timing of PBRM 1 mutations in biliary carcinogenesis. Methods and results In order to accomplish this goal, we used immunohistochemistry to assess PBRM 1 protein expression in a series of precursor lesions and invasive biliary carcinomas. Previous studies have correlated loss of protein expression on immunohistochemistry with inactivating mutations in this tumour suppressor gene. We found that PBRM 1 loss occurred in approximately 26% of invasive cancers, but PBRM 1 expression was retained in all biliary intra‐epithelial neoplasia (Bil IN ) specimens, including 25 intrahepatic Bil IN s and 19 gallbladder Bil IN s. Conclusions These findings indicate that PBRM 1 mutation (and resultant loss of expression) is a late event during biliary carcinogenesis. In addition, we confirm a lack of prognostic significance of PBRM 1 status in invasive intrahepatic cholangiocarcinoma. This study provides important insights into the basic mechanisms of chromatin remodelling genes in carcinogenesis.