Introduction: The presence of ROS1 gene rearrangements in lung cancers confers sensitivity to ROS kinase inhibitors, including crizotinib. However, they are rare abnormalities (~1% in non-small cell lung carcinoma), typically identified via FISH, and so screening using immunohistochemistry (IHC) would be both cost and time-efficient.
Methods: A cohort of lung tumours, negative for other common mutations related to targeted therapies, were screened to assess the sensitivity and specificity of IHC in detecting ROS1 gene rearrangements, enriched by four other cases first identified by FISH. A review of published data was also undertaken.
Results: IHC was 100% (95% CI 48-100) sensitive and 83% (95% CI 86-100) specific overall when an h-score of >100 was used. Patients with ROS1 gene rearrangements were younger and typically never smokers, with the tumours all adenocarcinomas with higher grade architectural features and focal signet ring morphology (2/5). Four patients treated with crizotinib showed partial response, with three also showing partial response to pemetrexed. Three of four patients remain alive at 13, 27 and 31 months respectively.
Conclusion: IHC can be used to screen for ROS1 gene rearrangements, with patients herein showing response to crizotinib. Patients with tumours positive with IHC but negative for FISH were also identified, which may have implications for treatment selection.