Better Selection Model for EML4-ALK Fusion Gene Test in Patients with Non-Small-Cell Lung Cancer

Dekel Shlomi, Amir Onn, Maya Gottfried, Jair Bar, Haim Biran, Maya Ilouze, Addie Dvir, Hovav Nechushtan, Lior Soussan-Gutman, Nir Peled

Oncology Department, Meir Medical Center, Kfar Saba, Israel.
Oncotest-TEVA, Teva Pharmaceutical Industries LTD., Shoham, Israel.
Pulmonary-Oncology Unit, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Sharett Institute of Oncology, Hadassah He- brew University Medical Center, Jerusalem, Israel..

DOI: 10.4236/jct.2013.48A009                

Abstract

Background: In the last decade, the search for gene mutations in lung cancer has been constantly growing. EGFR, KRAS mutations and, recently, the EML4-ALK fusion can guide the selection of treatment for patients who carry a specific mutation. Methods: During 2010-2011, EML4-ALK fusion test has been performed in Israel, mostly for wild type EGFR non-squamous NSCLC patients based on fluorescent in-situ hybridization (FISH) technique to detect EML4-ALK rearrangements. Results: Between January 2010 and December 2011, 3341 patients were diagnosed with lung cancer in Israel. Of the 2997 patients with NSCLC 687 had squamous cell carcinoma and 2310 had non-squamous NSCLC. This study focused on available 125 non-squamous NSCLC cases in which analysis for EML4-ALK rearrangement was available. All were negative for EGFR mutation. Nineteen (15.2%) were found positive for the fusion, a figure 2 - 10 times higher compared with previously reported findings. The EML4-ALK fusion was significantly more prevalent in younger male patients (52.1 vs. 61.3 years, p = 0.049), in whom every additional year reduced the chance to find the fusion by 7% [CI = 0.93 (0.88 - 0.99), p = 0.03]. Conclusions: A stepwise approach based on histology and prior EGFR analysis to detect EML4-ALK fusion is highly efficient with a related increased yield of detection. We recommend testing patients with non-squamous cell lung carcinoma after ruling out an EGFR mutation. The chance to find the ALK fusion is significantly greater in younger men.

Keywords

Lung Cancer; EML4-ALK; Gene Mutation; EGFR; Histology

Conflicts of Interest

The authors declare no conflicts of interest.

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