studies

386A AASLD ABSTRACTS HEPATOLOGY, October, 2015
347
Mutations of p53, ARID1A and KRAS mutations and
their association with “subtypes with stem-cell feature”
in combined hepatocellular-cholangiocellular carcinoma
Motoko Sasaki 1 , Yasunori Sato 1 , Yasuni Nakanuma 2,1 ; 1 Human
Pathology, Kanazawa University Graduate School of Medicine,
Kanazawa, Japan; 2 Shizuoka Cancer Center, Shizuoka, Japan
Backgrounds/Aims. Combined hepatocellular-cholangiocarcinoma
(cHC-CC) is composed of hepatocellular carcinoma
(HCC), cholangiocarcinoma (CC) and diverse components with
intermediate features between HCC and CC and is characterized
by poor prognosis. Subtypes with stem cell features (SC
subtype) including typical subtype (TS), intermediate cell subtype
(INT) and cholangiolocellular type (CLC) were proposed
in the WHO classification 2010. We have previously reported
that each SC subtype may have different clinicopathological
significance in cHC-CC. That is, the proportion of INT was significantly
correlated to histological grading of coexistent HCC
and tumor size, whereas the proportion of CLC was inversely
correlated to histological grading of coexistent HCC and
tumor size. In this study, we examined mutation status of p53,
ARID1A and KRAS and their association with clinicopathological
features, especially with SC subtypes, in cHC-CC. Methods.
Fifty-three patients with cHC-CC (14 women and 39 men, age
ranged 36-83 yrs, mean±SD, 65± 9.5yrs) were retrieved from
our pathological files (1996-2014). The background diseases
were hepatitis B (n=9), hepatitis C (21), chronic alcoholism or
nonalcoholic fatty liver disease (NAFLD) (8) and cryptogenic
(15). Mutations of p53, ARID1A and KRAS were also evaluated
using immunohistochemistry (p53, ARID1A) and direct
sequencing (KRAS). The prevalence of each component (HCC,
TS, INT, CLC and CC) was histologically assessed with assistance
of mucin staining and immunohistochemical staining
for CK7, CK19, EMA, EpCAM, NCAM, AFP and HepPar1.
Results: Mutations of p53, ARID1A and KRAS were detected
in 24 cases (45%), 7 (13%) and 4 of 39 (10%) respectively.
Mutations of both p53 and ARID1A were detected in 3 and
mutations of both p53 and KRAS were detected in 2 cHC-
CCs. SC subtypes were observed in all cHC-CCs in various
amount and combination. The prevalence of each SC subtype
in cHC-CC was as follows; TS, 8 (15%); INT, 33 (62%); and
CLC, 35 (66%). ARID1A-mutated cHC-CCs were significantly
smaller size (p