Zeta ROS1 Antibody. Zeta’s recombinant rabbit antibody recognizes ROS1 (Repressor of Silencing 1), an orphan receptor tyrosine kinase of the insulin receptor family, which was initially identified as a homolog of v-ros from the UR2 sarcoma virus. ROS1 consists of a large extracellular domain composed of six fibronectin repeats, a transmembrane domain, and an intracellular kinase domain. While the function of ROS1 is undefined, it has been shown to play an essential role in the differentiation of epididymal epithelium. The first oncogenic fusion of ROS1, FIG-ROS1, was initially identified by research studies in glioblastoma, and additional oncogenic ROS1 fusion proteins have been identified in NSCLC (at a frequency of ~1.6%), where the ROS1 kinase domain is fused to the amino-terminal region of a number of different proteins, including CD74 and SLC34A2. ROS1 gene rearrangements are reported in 1% to 2% of lung adenocarcinomas (Am J Surg Pathol 2013;37:554, Oncologist 2013;18:865), are associated with higher response rates to therapies including crizotinib (Ann Oncol 2013;24:2364, Clin Cancer Res 2012;18:4570).
Many laboratories currently rely on fluorescence in situ hybridization (FISH) assays using a dual-color break-apart probe to detect ROS1 rearrangements. Given the rarity of these rearrangements in NSCLC, detection of elevated ROS1 protein levels by immunohistochemistry may provide cost-effective screening prior to confirmatory FISH testing (Testing for ROS1 in non-small cell lung cancer: a review with recommendations – PMC (nih.gov)). IHC is an effective screening tool to detect ROS1+ NSCLC, with a sensitivity of 100% in most studies and a variable specificity ranging from 92%-100%, depending on the threshold used to define positivity. ROS1 IHC the advantage over FISH in that it can detect rare positive cells or cell groups within a majority of non-neoplastic reactive cells that would be easily missed by FISH. This can be particularly helpful in cytological specimens where architectural tissue context is lost.
Tumor specimens with known ROS1 rearrangement can serve as positive controls but there is currently no good external benign tissue control for ROS1.