ROS1, clone EPMGHR2

Immunohistochemical detection of ROS1 protein with the antibody ROS1, clone EPMGHR2 is an effective way to screen patient samples for the presence of activating ROS1 gene fusions. Those patients, with confirmed ROS1 translocation likely benefit from treatment with tyrosine kinase inhibitors such as crizotinib and ceritinib.

ROS1, a receptor tyrosine kinase (RTK), is a member of the family of insulin receptors with clear sequence homology and structural similarity to the anaplastic lymphoma kinase (ALK). The ROS1 gene is not expressed in most differentiated tissues and therefore the ROS1 protein is not detectable in most cases. Chromosomal rearrangements of the proto-oncogene result in gene fusions and subsequent expression of a chimeric protein with constitutive tyrosine kinase activity. This has been shown to contribute to the development of various tumors, such as non-small cell lung cancer (NSCLC) [1].  The prevalence of ROS1 fusions in NSCLC is approximately 1- 2 %.  
Clinical studies and case reports show that treatment with tyrosine kinase inhibitors such as crizotinib and ceritinib represents an effective therapeutic strategy in patients with activating ROS1 rearrangements [2,3]. Due to the low incidence of ROS1 translocations, immunohistochemical detection of the ROS1 protein is an effective tool to screen patient samples for the presence of activating ROS1 fusions. In any case, verification of the results using FISH or molecular analysis is recommended, especially in cases of weak and/or focal immunohistochemical staining. A number of studies have shown a good correlation between ROS1 FISH and ROS1 IHC with reported sensitivities of 94 % to 100 % and specificities of 76 % to 100 %. [4-6].
The establishment of a ROS1 immunohistochemistry as well as its routine use in diagnostics requires a validated process using appropriate controls [4].  The Cell Control Array ROS1 (IHC) block serves as a positive control for the detection of ROS1 protein in lung and other tissues. It is a homogenous paraffin block including two ROS1 positive cell lines, one ROS1 negative cell line, and one core of heart muscle tissue. The two positive ROS1 cell lines differ in their level of ROS1 expression, showing weak and medium expression, respectively.


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ROS1, clone EPMGHR2

ROS1, a receptor tyrosine kinase (RTK), is a member of the family of insulin receptors with clear sequence homology and structural similarity to the anaplastic lymphoma kinase (ALK).

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Products

Primary antibodies

Product Cat. no. Amount Status Info
ROS1 RBK071-01 0,1 ml RUO
ROS1 RBK071-05 0,5 ml RUO
ROS1 RBG071 6 ml RUO

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Cell control arrays

Product Cat. no. Amount Status Info
Cell Control Array ROS1 (IHC) MB-CC ROS1 1 Block RUO

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Bibliography

[1] Uguen A, de Brakeleer M. ROS1 fusions in cancer: a review. Future Oncol 12:1911-1928, 2016
[2] Mazières J et al. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort. J Clin Oncol 33:992-999, 2015
[3] Shaw AT et al. Crizotinib in ROS1-rear-ranged non-small-cell lung cancer. N Engl J Med 371:1963-1971, 2014
[4] Bubendorf L et al. Testing for ROS1 in non-small cell lung cancer: a review with recommendations. Virchows Arch 469:489-503, 2016
[5] Selinger CI et al. Screening for ROS1 gene rearrangements in non-small-cell lung cancers using immunohis-tochemistry with FISH confirmation is an effective method to identify this rare target. Histopathology 70:402– 411, 2017
[6] Luk P et al. Biomarkers for ALK and ROS1 in Lung Cancer. Arch Pathol Lab 142: 922-928, 2018


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