Abstract
BackgroundMore knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies. We investigated the clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma.MethodsOne hundred ninety-four patients with curatively resected intrahepatic cholangiocarcinoma were included in this study. Tumor tissue specimens were collected and analyzed for ROS1 gene rearrangement using fluorescence in situ hybridization (FISH) and ROS1 protein expression using immunohistochemistry (IHC).ResultsROS1 immunohistochemistry was positive (moderate or strong staining) in 72 tumors (37.1 %). ROS1 protein expression was significantly correlated with well differentiated tumors, papillary or mucinous histology, oncocytic/hepatoid or intestinal type tumors, and periductal infiltrating or intraductal growing tumors (vs. mass-forming cholangiocarcinoma). ROS-expressing tumors were associated with better disease-free survival (30.1 months for ROS1 expression (+) tumors vs. 9.0 months for ROS1 (−) tumors, p = 0.006). Moreover, ROS1 expression was an independent predictor of better disease-free survival in a multivariate analysis (HR 0.607, 95 % CI 0.377–0.976; p = 0.039). Although break-apart FISH was successfully performed in 102 samples, a split pattern indicative of ROS1 gene rearrangement was not found in the examined samples.ConclusionROS1 protein expression was associated with well-differentiated histology and better survival in our patients with resected intrahepatic cholangiocarcinoma. ROS1 gene rearrangement by break-apart FISH was not found in the examined samples.
Highlights
More knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies
Intrahepatic cholangiocarcinoma is a distinct disease with increasing incidence in the western countries and worldwide, and its etiology and molecular pathogenesis differs from the other Biliary tract cancer (BTC) [2]
We aimed to investigate both protein expression and gene fusion of ROS1 in a larger number of patients with intrahepatic cholangiocarcinoma
Summary
More knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies. We investigated the clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma. Biliary tract cancer (BTC) is an aggressive disease with a very poor prognosis with a median survival of less than 1 year [1]. It is a heterogeneous group of disease including intrahepatic, perihilar, or distal cholangiocarcinoma and gallbladder cancer, with diverse epidemiology, etiology, and pathogenesis. Intrahepatic cholangiocarcinoma is a distinct disease with increasing incidence in the western countries and worldwide, and its etiology and molecular pathogenesis differs from the other BTCs [2]. Five-year survival rate after curative surgery for intrahepatic cholangiocarcinoma remains poor.
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