Immunohistochemical Detection of ROS1 Fusion.

Objectives: Patients whose tumors harbor ROS1 translocation may benefit from targeted therapy. Detection of ROS1 rearrangement can be done by three methods: immunohistochemistry, fluorescence in situ hybridization, and molecular assays. Immunohistochemistry would be a cost-effective means to screen for ROS1 translocation, which is uncommon. Methods: ROS1 immunostain was performed on cases with known ROS1 translocation status detected either by fluorescence in situ hybridization or next-generation sequencing. Results: Fifty-seven cases, 10 lung carcinomas with ROS1 rearrangement and 47 cases without ROS1 rearrangement (25 lung carcinomas, 13 gastrointestinal carcinomas, three brain tumors, and six miscellaneous tumors), were included. ROS1 immunostain exhibited 100% sensitivity and 85% specificity, with staining seen in 10 (100%) of 10 cases with ROS1 rearrangement and in seven (15%) of 47 lung cases without ROS1 rearrangement. Weak or 1+ staining of reactive pneumocytes was seen in eight (14%) of 57 cases, and strong staining of osteoclast giant cells was seen in one case. Conclusions: Since ROS1 rearrangement is an infrequent event, immunohistochemistry is a cost-effective screening method. Confirmation of all positive and equivocal/weak staining with molecular assays would exclude the false positive cases.