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Cholangiocarcinoma Heterogeneity Revealed by Multigene Mutational Profiling: Clinical and Prognostic Relevance in Surgically Resected Patients
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Cholangiocarcinoma Heterogeneity Revealed by Multigene Mutational Profiling: Clinical and Prognostic Relevance in Surgically Resected Patients
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Journal Article
Cholangiocarcinoma Heterogeneity Revealed by Multigene Mutational Profiling: Clinical and Prognostic Relevance in Surgically Resected Patients
2016
Overview
Background
Cholangiocarcinoma can be classified in intrahepatic cholangiocarcinoma (ICC) and perihilar cholangiocarcinoma (PCC). Moreover, PCC includes two different forms: extrahepatic (EH) PCC, which arises from the perihilar EH large ducts, and intrahepatic (IH) PCC, in which a significant liver mass invades the perihilar bile ducts. In this study, we investigated the molecular profile and molecular prognostic factors in EH-PCC, IH-PCC, and ICC submitted to curative surgery.
Methods
Ninety-one patients with cholangiocarcinoma (38 EH-PCC, 18 IH-PCC, and 35 ICC), who underwent curative surgery in a single tertiary hepatobiliary surgery referral center were assessed for mutational status in 56 cancer-related genes.
Results
The most frequently mutated genes in EH-PCC were
KRAS
(47.4 %),
TP53
(23.7 %) and
ARID1A
(15.8 %); in IH-PCC were
KRAS
(22.2 %),
PBRM1
(16.7 %), and
PIK3CA
(16.7 %); and in ICC were
IDH1
(17.1 %),
NRAS
(17.1 %), and
BAP1
(14.3 %). The presence of mutations in
ALK
,
IDH1
, and
TP53
genes was significantly associated with poor prognosis in patients with EH-PCC (
p
< 0.001,
p
= 0.043, and
p
= 0.019, respectively). Mutation of the
TP53
gene was significantly associated with poor prognosis in patients with IH-PCC (
p
= 0.049). The presence of mutations in
ARID1A
,
PIK3C2G
,
STK11
,
TGFBR2
, and
TP53
genes was significantly associated with poor prognosis in patients with ICC (
p
= 0.012,
p
= 0.030,
p
= 0.030,
p
= 0.011, and
p
= 0.011, respectively).
Conclusions
Mutational gene profiling identified different gene mutations in EH-PCC, IH-PCC, and ICC. Moreover, our study reported specific prognostic genes that can identify patients with poor prognosis after curative surgery who may benefit from traditional or target adjuvant treatments.
Publisher
Springer International Publishing,Springer Nature B.V
Subject
/ Aged
/ Bile Duct Neoplasms - genetics
/ Bile Duct Neoplasms - pathology
/ Bile Duct Neoplasms - surgery
/ Bile Ducts, Extrahepatic - metabolism
/ Bile Ducts, Extrahepatic - pathology
/ Bile Ducts, Extrahepatic - surgery
/ Bile Ducts, Intrahepatic - metabolism
/ Bile Ducts, Intrahepatic - pathology
/ Bile Ducts, Intrahepatic - surgery
/ Biomarkers, Tumor - genetics
/ Cholangiocarcinoma - genetics
/ Cholangiocarcinoma - pathology
/ Cholangiocarcinoma - surgery
/ Female
/ High-Throughput Nucleotide Sequencing - methods
/ Humans
/ Male
/ Medicine
/ Oncology
/ Surgery
