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Published on: August 11, 2017
EML4-ALK translocation predicts better outcome in lung adenocarcinoma patients with wild-type EGFR
Shang-Gin Wu1, Yao-Wen Kuo, Yih-Leong Chang
1Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.
Introduction:
The echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion represents a novel target in a subset of non-small cell lung cancer, especially adenocarcinoma. EML4-ALK fusion is mutually exclusive with epidermal growth factor receptor (EGFR) mutations. To understand the impact of EML4-ALK on the prognosis of non-small cell lung cancer, we examined EML4-ALK fusion in lung adenocarcinoma from patients with wild-type EGFR and analyzed their clinical treatment outcomes.
Methods:
Lung adenocarcinoma patients with malignant pleural effusions having wild-type EGFR and measurable target lesions were enrolled for EML4-ALK analysis by reverse transcription-polymerase chain reaction and direct sequencing. Demographic data, EML4-ALK status, and survival data were analyzed. We also performed fluorescence in situ hybridization on some available tumor samples to validate the PCR result. In addition, K-ras mutation was analyzed for patients without EML4-ALK fusion genes.
Results:
A total of 116 patients with wild-type EGFR sequencing results had complete clinical data for analysis. No patients received ALK inhibitor therapy. There were 39 patients (34%) with the EML4-ALK fusion gene. The concordance rate between reverse transcription-polymerase chain reaction and fluorescence in situ hybridization was 85%. The K-ras mutation rate for patients without EML4-ALK fusion gene was 6.5%. By multivariate analysis, patients who had better performance status (p < 0.001) and EML4-ALK translocation (p = 0.017) had longer overall survival. Comparing patients with tumors harboring variant 1 with those harboring nonvariant 1 EML4-ALK fusion genes, there were no significant differences in clinical factors and survival outcome.
Conclusion:
For lung adenocarcinoma patients with wild-type EGFR, EML4-ALK translocation is associated with longer overall survival.
Insights
Echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion in lung adenocarcinoma with wild-type EGFR is linked to improved survival. This finding offers insights into non-small cell lung cancer prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) harbors specific molecular targets, including echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusions.
- EML4-ALK fusions are frequently observed in lung adenocarcinoma and are mutually exclusive with epidermal growth factor receptor (EGFR) mutations.
- Understanding the prognostic significance of EML4-ALK fusions in EGFR wild-type NSCLC is crucial for treatment strategies.
Purpose of the Study:
- To investigate the impact of EML4-ALK fusion on the clinical outcomes of lung adenocarcinoma patients with wild-type EGFR.
- To analyze the association between EML4-ALK translocation and overall survival in this patient cohort.
Main Methods:
- Retrospective analysis of 116 lung adenocarcinoma patients with wild-type EGFR and malignant pleural effusions.
- EML4-ALK fusion detection using reverse transcription-polymerase chain reaction (RT-PCR) and direct sequencing.
- Validation of RT-PCR results with fluorescence in situ hybridization (FISH) and analysis of K-ras mutations in EML4-ALK negative cases.
Main Results:
- EML4-ALK fusion was detected in 34% of the analyzed patients.
- Multivariate analysis revealed that EML4-ALK translocation was significantly associated with longer overall survival (p = 0.017).
- Better performance status also correlated with improved survival (p < 0.001).
Conclusions:
- EML4-ALK translocation is a favorable prognostic marker in lung adenocarcinoma patients with wild-type EGFR.
- The presence of EML4-ALK fusion suggests a potentially better prognosis, independent of EGFR status.
