studies

1136A AASLD ABSTRACTS HEPATOLOGY, October, 2015
1901
ARID1A mutations may represent a novel pathway of
carcinogenesis in biliary carcinomas
Motoko Sasaki 1 , Takeo Nitta 2 , Yasunori Sato 1 , Yasuni
Nakanuma 3 ; 1 Human Pathology, Kanazawa University Graduate
School of Medicine, Kanazawa, Japan; 2 Gastroenterological
Surgery II, Hokkaido University Graduate School of Medicine,
Sapporo, Japan; 3 Division of Pathology, Shizuoka Cancer Center,
Shizuoka, Japan
Backgrounds/Aims. We have reported that some cholangiocarcinoma
arise following a stepwise pathway of carcinogenesis
through flat and papillary premalignant lesions, biliary intraepithelial
neoplasia (BilIN) and intraductal papillary neoplasm of
the bile duct (IPNB) and KRAS mutations and GNAS mutations
may be involved in this pathway. Recent studies using exome
sequencing and next generation sequencing revealed frequent
alterations in several new genes including the three chromatin-remodeling
genes (BAP1, ARID1A or PBRM) in cholangiocarcinomas.
Given frequent inactivating mutations in ARID1A
gene coding BAF250a protein in intrahepatic cholangiocarcinoma
and a reported usefulness of ARID1A/BAF250a immunostaining
to detect ARID1A mutation, this study investigates
immunohistochemically the clinicopathological significance of
ARID1A mutations in biliary carcinomas. Methods. We examined
the status of inactivating mutations in ARID1A by immunohistochemistry
and the relationship with clinicopathological
features in 13 patients with combined hepatocellular-cholangiocarcinoma
(cHC-CC, M/F=9/4), 49 patients with intrahepatic
cholangiocarcinoma (ICC, M/F=22/27), 17 with IPNB (M/
F=11/6), 72 with extrahepatic cholangiocarcinoma (EHCC,
M/F=51/21) and 43 with gallbladder carcinoma (GBC, M/
F=18/25). Fifteen BilIN lesions were also examined. Results.
Complete loss or clonal loss of ARID1A immunoreactivity indicating
the inactivating mutations of ARID1A was detected in
one (7.7%) of cHC-CC, 9 (18.4%) of ICC, none of IPNB, 11
(15.3%) of EHCC and 4 (9.1%) of GBC. The patients with
biliary carcinoma with ARID1A mutations were significantly
female-predominant (p