Detection of ROS1 rearrangement in non-small cell lung cancer: current and future perspectives

<i>ROS1</i> rearrangement characterizes a small subset (1%-2%) of non-small cell lung cancer and is associated with slight/never smoking patients and adenocarcinoma histology. Identification of <i>ROS1</i> rearrangement is mandatory to permit targeted therapy with specific inhibitors, demonstrating a significantly better survival when compared with conventional chemotherapy. Detection of <i>ROS1</i> rearrangement is based on in situ (immunohistochemistry, fluorescence in situ hybridization) and extractive non-in situ assays. While fluorescence in situ hybridization still represents the gold standard in clinical trials, this technique may fail to recognize rearrangements of <i>ROS1</i> with some gene fusion partner. On the other hand, immunohistochemistry is the most cost-effective screening technique, but it seems to be characterized by low specificity. Extractive molecular assays are expensive and laborious methods, but they specifically recognize almost all <i>ROS1</i> fusions using a limited amount of mRNA even from formalin-fixed, paraffin-embedded tumor tissues. This review is a discussion on the present and futuristic diagnostic scenario of <i>ROS1</i> identification in lung cancer.