Rare Incidence of Rearrangement in Cholangiocarcinoma.

Purpose: The recent discovery and characterization of an oncogenic gene rearrangement has raised significant interest because small molecule inhibitors are effective in these tumors. The aim of this study was to determine frequency and clinicopathological features associated with rearrangement in patients with cholangiocarcinoma (CCA).

Materials And Methods: A total of 261 patients who underwent surgery for CCA between October 1997 and August 2013 were identified from an international, multi-institutional database. rearrangement was evaluated by break-apart fluorescence hybridization using tissue microarrays of these patients.

Results: Of 261 CCA evaluated, three cases (1.1%) showed rearrangement by fluorescence hybridization (FISH), all of which were derived from intrahepatic origin. ROS1 protein expression was observed in 38 samples (19.1%). Significantly larger tumor size was observed in ROS1 immunohistochemistry (IHC)-negative patients compared with ROS1 IHC-positive patients. FISH-positive patients had a single tumor with a median size of 4 cm and well-to-moderate differentiation. Overall, there was no difference in terms of baseline characteristics, overall survival, and recurrence-free survival between -positive and -negative patients.

Conclusion: rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.