ALK-Positivity Prevalence on Immunohistochemistry and FISH in Resected Stage I to III Lung Adenocarcinoma
The European Thoracic Oncology Platform Lungscape ALK project is investigating the prevalence and prognostic impact of ALK-positivity in resected lung adenocarcinoma in a primarily European population. As reported in the Journal of Clinical Oncology by Blackhall and colleagues, the project has found a prevalence of 6.1% on immunohistochemistry and ≥ 2.2% on fluorescence in situ hybridization (FISH) in resected stage I to III disease and has confirmed that ALK-positivity on either immunohistochemistry or FISH is predictive of better overall survival.
In the study, ALK status was assessed by immunohistochemistry and FISH in samples from 1,281 patients in 16 centers. ALK-positive patients were matched with ALK-negative patients in a 1:2 ratio for both methods.
Prevalence
Overall, 80 patients (6.2%, 95% confidence interval [CI] = 4.9%–7.6%) were ALK-positive on immunohistochemistry staining. Of these, 28 were ALK-positive on FISH, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH had a specificity of 100% and a sensitivity of 35.0% (95% CI = 24.7%–46.5%); FISH sensitivity in immunohistochemistry 2+/3+ patients was 81.3% (95% CI = 63.6%–92.8%).
Association With Outcomes
Median follow-up was 57.1 months. Patients who were immunohistochemistry ALK-positive vs -negative had significantly better median overall survival (not reached vs 69.5 months, hazard ratio [HR] = 0.61, P = .012), relapse-free survival (HR = 0.65, P = .018), and time to relapse (HR = 0.60, P = .015). Compared with ALK immunohistochemistry-negative (presumed FISH-negative) patients, ALK FISH- and immunohistochemistry-positive patients had a significant improvement only in overall survival (5-year overall survival = 73.4% vs 54.4%, P = .022).
After adjustment for factors of clinical interest, ALK immunohistochemistry-positive/FISH-positive patients had significantly better overall survival (HR = 0.42, P = .025) and nonsignificantly better relapse-free survival (HR = 0.63, P = .11) and time to relapse (HR = 0.64, P =.17) compared with ALK immunohistochemistry-negative patients.
The investigators concluded: “In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK-positivity was 6.2% using [immunohistochemistry] and at least 2.2% using FISH. A screening strategy based on [immunohistochemistry] or H-score could be envisaged. ALK positivity (by either [immunohistochemistry] or FISH) was related to better overall survival.”
Rolf A. Stahel, MD, of University Hospital Zurich, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Pfizer, Abbott Molecular, and F. Hoffmann La Roche. For full disclosures of the study authors, visit jco.ascopubs.org.
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