Start Your Search
Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Presentations: 1
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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 | Presenting Author(s): G. Metro
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:
Has not received any funding
All authors have declared no conflicts of interest.
Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.