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D. Giannarelli

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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      27P - ALK immunohistochemistry scores do not predict sensitivity to crizotinib in fluorescence in situ hybridization-positive non-small cell lung cancer patients (ID 512)

      12:30 - 13:00  |  Author(s): D. Giannarelli

      • Abstract
      • Slides

      Anaplastic lymphoma kinase (ALK) immunohistochemistry (IHC) is an established screening method for the detection of ALK gene rearrangements by fluorescence in situ hybridization (FISH) in patients with advanced non-small cell lung cancer. However, little is known about the correlation between ALK IHC scores and sensitivity to treatment with an ALK-tyrosine kinase (-TKI) inhibitor.

      ALK IHC score was evaluated through a 4-tiered system (0, 1+, 2+, 3+) based on the D5F3 clone (Cell Signaling). Any number of cells stained was considered as ALK positive, and the strongest staining present was the final score. H-score was assessed using the following formula: [1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)] resulting into a score from 0 to 300. All ALK IHC score positive tumors underwent confirmatory FISH (Vysis ALK Break Apart Probe kit).

      From June 2011 to May 2017, 50 double ALK IHC/FISH-positive patients were identified at our Institution. The majority of patients had an ALK IHC score ≥2+ [5/50 (10%) score 1+; 23/50 (46%) score 2+; 22/50 (44%) score 3+], with 47/50 (94%) tumors having any ALK IHC positivity in ≥50% of cells. H-score was more commonly ≥100 [2/50 (4%) 1-<100; 14/50 (28%) ≥100-<200; 34/50 (68%) ≥200–300]. Overall, 31 patients were treated with the ALK-TKI crizotinib for advanced disease, whose main charachteristics were as follows: median age 50 years (28–80), male/female (42%/58%), never/ever smokers (61%/39%), performance status 0/1 (74%/26%), chemotherapy-pretreated (90%). The results showed no significant correlation between the intensity of ALK IHC score or H-score with regard to response to crizotinib. Similarly, no significant association was noted between the intensity of ALK IHC score as well as the H-score and progression-free survival.

      In double ALK IHC/FISH-positive patients ALK IHC scores are typically skewed towards higher values, and ALK protein is expressed in a mostly diffuse way. Such preferentially higher distribution of ALK IHC scores as well as diffuse ALK staining might imply difficulty in setting a discriminatory treshold of activity with regard to sensitivity to crizotinib. This, in turn, could justify the absence of predictivity of ALK IHC scores.

      Clinical trial identification:

      Legal entity responsible for the study:
      Giulio Metro

      Has not received any funding

      All authors have declared no conflicts of interest.

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