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K. Ellison

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-004 - ROS1 Immunohistochemistry Among Major Genotypes of Non-Small Cell Lung Carcinoma (ID 739)

      09:30 - 16:30  |  Author(s): K. Ellison

      • Abstract

      ROS1 (c-ros oncogene 1) is a receptor tyrosine kinase that can become constitutively active and drive cellular proliferation in a variety of cancers. Approximately 1-2% of patients with non-small cell lung cancer (NSCLC) harbor activating ROS1 gene fusions and these patients may benefit from ROS1-targeted inhibitor therapy.

      Immunohistochemistry for ROS1 expression was performed on 33 NSCLC specimens previously characterized for the presence of genetic abnormalities. These specimens were selected for ROS1 gene rearrangements (6 specimens) detected by RT-PCR and FISH, ALK gene rearrangements (5 specimens), EGFR mutations (5 specimens), KRAS mutations (5 specimens), HER2 mutations (3 specimens), RET gene rearrangements (3 specimens), and pan-negative (6 specimens). Immunohistochemistry was performed in a CLIA-certified laboratory with manual application of the ROS1 DFD6 antibody (Cell Signaling Technology, Inc) for 1 hour. ROS1 protein expression was evaluated by a pathologist with a hybrid (H)-score scale of 0 (no expression in any tumor cells) to 300 (intense expression in all tumor cells). ROS1 over-expression was defined as an H-score greater than 100.

      ROS1 protein over-expression was detected by immunohistochemistry in all 6 of the NSCLC specimens with ROS1 gene fusions detected by RT-PCR (example in figure below). None of the remaining 27 lung cancer specimens with ALK gene rearrangements, EGFR mutations, KRAS mutations, HER2 mutations, RET gene rearrangements, or pan-negative exhibited ROS1 protein over-expression. Figure 1

      Detection of ROS1 over-expression by immunohistochemistry exhibited 100% concordance with results of ROS1 gene rearrangement for 33 NSCLC specimens and did not overlap with any of the other genetic alterations. Six specimens were positive for ROS1 gene rearrangement by both RT-PCR and immunohistochemistry. Tumors positive for genetic alterations associated with the ALK, EGFR, KRAS, HER2, and RET genes were all negative for ROS1 gene rearrangement and ROS1 immunohistochemistry. ROS1 immunohistochemistry is a sensitive, specific and cost-effective method for identification of a subset of patients with lung cancer that may benefit from ROS-1 targeted-therapy.