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L. Bubendorf



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    Targeted therapies and management of brain metastasis (ID 40)

    • Event: ELCC 2017
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
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      1O - ROS1 immunocytochemistry on cytological specimens in patients with non-small cell lung cancer (ID 503)

      16:45 - 18:15  |  Author(s): L. Bubendorf

      • Abstract
      • Slides

      Background:
      Rearrangements of the ROS1 gene are found in 1-2% of non-small cell lung cancers (NSCLC) and are regarded as mutually exclusive oncogenic driver mutations. Since targeted therapy has recently been approved for ROS1-positive NSCLC, ROS1 testing is entering diagnostic routine. Fluorescence in situ hybridization (FISH) optionally selected for by immunohistochemistry (IHC) on histological material is regarded as gold standard for detection of ROS1 rearrangements. However, NSCLC is often diagnosed by cytology alone, requiring the option of predictive marker testing on cytological specimens. In this study, we explored the utility of ROS1 immunocytochemistry (ICC) on cytological specimens as a preliminary screening tool for detection of ROS1 rearrangements.

      Methods:
      ICC using the D4D6 antibody was prospectively performed in the routine diagnostic setting on ethanol-fixed and previously Papanicolaou-stained specimens from 296 patients with NSCLC, including adenocarcinomas (n = 243), NSCLC NOS (n = 47), and others (n = 6) and encompassing specimens from the lung (n = 107), locoregional lymph nodes (n = 87) and distant metastases (n = 102). Cytospin specimens of the cell line HCC-78, known to express ROS1, were used as positive control. Cytoplasmic staining of any intensity was considered positive.

      Results:
      ICC was positive in 12 cases with ROS1 rearrangements confirmed by FISH. Confirmation of 284 ICC-negative cases was available in 210 cases (FISH in 71 cases, mRNA based fusion NGS in 2 cases and detection of other known, mutually exclusive driver mutations in 137 cases). Only one ICC-negative case showed a ROS1 rearrangement by FISH (sensitivity 92%, specificity 100%, PPV 100%, NPV 99%).

      Conclusions:
      Our data show that ROS1 ICC is a highly accurate method for detection of ROS1 rearrangements in NSCLC. Given the high costs and technical challenges of FISH and the rarity of ROS1 rearrangements, ICC is cost effective and rapid and therefore well suited as a preliminary screening method. Cases with equivocal or positive findings on ICC can be confirmed by FISH or molecular tests (e.g. NGS).

      Clinical trial identification:


      Legal entity responsible for the study:
      University Hospital Basel

      Funding:
      University Hospital Basel

      Disclosure:
      All authors have declared no conflicts of interest.

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