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Z. Dastani



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    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.02-055 - Detecting ALK, ROS1 and RET Gene Translocations in Non-Small Cell Lung Cancer (NSCLC) with the NanoString Platform (ID 9976)

      09:30 - 09:30  |  Author(s): Z. Dastani

      • Abstract
      • Slides

      Background:
      Identification of ALK, ROS1 and RET fusions is critical for guiding target therapy of lung cancers. In this study, we evaluated the transcript-based nanoString assay for detection of ALK fusions compared to immunohistochemistry (IHC) and FISH methods, and the simultaneous detection of ROS1 and RET transcripts in formalin-fixed and paraffin embedded tissues (FFPE).

      Method:
      A total of 44 patients with NSCLC were selected for this non-consecutive case study. Samples included 24 cases of non-smokers or patients younger than 50 years with negative EGFR/ALK results that are more likely to contain a ROS1 or RET translocation. Eight cases with a discrepancy between ALK IHC and FISH results or equivocal IHC ALK results, as well as 12 cases previously confirmed positive for ALK by IHC were also included. The specimens were assessed for ALK, ROS1 and RET fusion transcripts by nanoString nCounter profiling.

      Result:
      While nanoString demonstrated 94.9% concordance with IHC and 84.2% concordance with FISH, it detected unknown ALK active transcripts in 3 of 7 cases that showed a discrepancy between IHC and FISH, or which were negative for ALK by IHC and FISH (see table 1). The three equivocal ALK IHC cases were scored negative by the 2 other methods. In addition to ALK, 3 cases of ROS1 and 2 cases of RET fusions were detected by nanoString. ALK, ROS1 and RET fusions were found mutually exclusive. Table 1. Discrepancy of ALK findings by IHC, FISH and nanoString, and crizotinib response

      Case IHC FISH FISH positive nuclei (%) nanoString Crizotinib response
      1 Positive Negative 3.9 Unknown ALK active fusion Positive
      2 Negative Negative 3.3 Unknown ALK active fusion Positive
      3 Negative Negative 8.6 Unknown ALK active fusion Unknown
      4 Negative Borderline 17.3 Negative Not treated
      5 Negative Borderline 15.1 Negative Not treated
      6 Negative Borderline 19.7 Negative Not treated
      7 Negative Positive 24 Inconclusive Unknown


      Conclusion:
      NanoString performed well in lung cancer FFPE tissue including cytology materials. The results are highly concordant with the current standard methods of ALK-1 IHC and FISH. As a single test, it detected ALK, ROS1 and RET fusions simultaneously. NanoString profiling can be an alternative for a one tube test for ALK, ROS1 and RET translocations in a selected NSCLC patient group.

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