Abstract 3481
Background
Biliary tract cancer (BTC) is a heterogeneous group of cancers anatomically divided into gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). None of molecular target agents has been proven to improve the prognosis of BTC yet. To gain a deeper understanding of BTC’s pathophysiology and find its new potential therapeutic targets, this study aims to investigate genetic profiles of BTC and their clinical implication.
Methods
A total of 124 patients with adenocarcinoma of biliary tract from Jan 2014 to Feb 2018 were enrolled. With DNA specimen extracted from previously-collected tumor tissue, somatic mutation and copy number analyses were performed using targeted exome sequencing. Data regarding baseline patient characteristics and treatment outcomes were retrospectively obtained from medical records.
Results
Twenty-five patients with GBC (20.2%), 55 with ICC (44.4%) and 44 with ECC (35.5%) were included in the analysis. Genetic mutation were observed in 104 patients (83.8%) and the rest 20 (16.1%) did not have any genetic alterations. The most commonly mutated gene was TP53 (n = 55, 44.4%), followed by KRAS (n = 36, 29.0%), ARID1A (n = 15, 12.1%) and IDH1 (n = 12, 9.7%). IDH1/2 mutation appeared more frequently in ICC (n = 12, 21.8%, P = 0.012) compared to GBC (n = 1, 4.0%) or ECC (n = 1, 2.3%) while ERBB2 and ERBB3 mutation were found only in GBC and ECC. ERBB2 amplification was observed in 7 patients (4 with GBC and 3 with ICC). Among those, one patient showed 3+ for HER2 test by immunohistochemistry (IHC) while four patients were 2+. Survival outcomes were analyzed among 122 patients who had eventually received palliative chemotherapy for their advanced disease. Patients harboring TP53 mutation had shorter PFS (5.7 vs. 7.1 months, P = 0.08) and OS (15.2 vs. 37.8 months, P = 0.03) compared to those without TP53 mutation, while IDH1 mutation was likely to be related to favorable PFS (10.6 vs. 6.1 months, P = 0.069). On the other hand, there were no significant differences in PFS or OS depending on KRAS or ARID1A mutation.
Conclusions
Genetic profile of BTC is heterogeneous according to its anatomic location. Our results indicate that subgroup of BTC may benefit from targeted therapy such as anti-IDH and anti-HER2 inhibitor.
Clinical trial identification
Legal entity responsible for the study
Institutional Review Board of the Asan Medical Center.
Funding
Has not received any funding.
Editorial Acknowledgement
None
Disclosure
All authors have declared no conflicts of interest.
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