Multigene mutational profiling of biliary tract cancer is related to the pattern of recurrence in surgically resected patients

The aim of the present study was to investigate the relationship between the mutational gene profile and recurrence in biliary tract cancers (BTC). A total of 103 specimens of patients with BTC, who underwent curative surgery in a single tertiary HPB surgery referral center from 1990 to 2012, were assessed for mutational status in 52 cancer-related genes. Considering the different types of BTC, the 5-year recurrence-free survival (RFS) rate was 16.7% (median RFS 7 months) in gallbladder cancer, 42.9% (median RFS 26.4 months) in intrahepatic cholangiocarcinoma, and 19.7% (median RFS 16.5 months) in perihilar cholangiocarcinoma, p = 0.166. At the multivariate analysis including clinical, pathological, and molecular features, the factors independently related to RFS were radicality of surgery (OR 2.050, CI 1.104–3.807, p = 0.023), LN status (OR 1.835, CI 1.006–3.348, p = 0.048), mutational status of ARID1A (OR 2.566, CI 1.174–5.608, p = 0.018), and TP53 (OR 2.805, CI 4.432–5.496, p = 0.003). ARID1A mutation was associated with a local and systemic recurrence in the 43% and 29% of cases, respectively; and TP53 mutation was associated with a local and systemic recurrence in the 29% and 41% of cases. Moreover, TP53 was most commonly mutated in tumor of patients with early recurrence, p = 0.044. ARID1A and TP53 mutations seem to be related to poor outcome after surgery and may be considered molecular predictors of the biological aggressiveness in BTC.