rearrangements are uncommon in biliary tract cancers.

Biliary tract cancers (BTCs) are a pool of diseases with poor prognosis and there is no orphan drug available. Currently, no molecular targets have been tested as druggable oncogenic drivers. C-ros oncogene 1 () rearrangements have been previously described in various tumors, including BTCs; however, data regarding their incidence and biological significance are controversial. Therefore, a retrospective multicenter study was performed to assess the incidence of rearrangements in BTCs by means of immunohistochemistry and fluorescence hybridization (FISH). The present study failed to demonstrate ROS1 expression in a multicenter series of 150 cases with BTCs and revealed that D4D6 was the most specific clone compared with other ROS1 primary antibodies, namely PA1-30318 and EPMGHR2. Notably, negative results obtained with D4D6 completely matched to data sorted out by FISH analysis, thus confirming a lack of gene rearrangements in BTCs and false positive results when PA1-30318 and EPMGHR2 clones were used. These results suggest that rearrangements may not be targets for molecular therapy of BTCs with specific inhibitors.