Abstract
The EML4-ALK fusion gene has been recently identified in a small subset of non-small cell lung cancer (NSCLC) patients who respond positively to ALK inhibitors. The characteristics of the EML4-ALK fusion gene in Chinese patients with NSCLC are poorly understood. Here, we report on the prevalence of EML4-ALK, EGFR status and KRAS mutations in 208 Chinese patients with NSCLC. EGFR mutations were found in 24.5% (51/208) of patients. In concordance with previous reports, these mutations were identified at high frequencies in females (47.5% vs 15.0% in males; P<0.05); never-smokers (42.3% vs 13.9% in smokers; P<0.05), and adenocarcinoma patients (44.2% vs 8.0% in non-adenocarcinoma patients; P<0.05). There were only 2.88% (6/208) patients with KRAS mutations in our study group. We identified 7 patients who harbored the EML4-ALK fusion gene (3.37%, 7/208), including 4 cases with variant 3 (57.1%), 2 with variant 1, and 1 with variant 2. All positive cases corresponded to female patients (11.5%, 7/61). Six of the positive cases were non-smokers (7.69%, 6/78). The incidence of EML4-ALK translocation in female, non-smoking adenocarcinoma patients was as high as 15.2% (5/33). No EGFR/KRAS mutations were detected among the EML4-ALK positive patients. Pathological analysis showed no difference between solid signet-ring cell pattern (4/7) and mucinous cribriform pattern (3/7) in ALK-positive patients. Immunostaining showed intratumor heterogeneity of ALK rearrangement in primary carcinomas and 50% (3/6) of metastatic tumors with ALK-negative staining. Meta-analysis demonstrated that EML4-ALK translocation occurred in 4.84% (125/2580) of unselected patients with NSCLC, and was also predominant in non-smoking patients with adenocarcinoma. Taken together, EML4-ALK translocations were infrequent in the entire NSCLC patient population, but were frequent in the NSCLC subgroup of female, non-smoker, adenocarcinoma patients. There was intratumor heterogeneity of ALK rearrangement in primary carcinomas and at metastatic sites.
Highlights
Lung cancer is a leading cause of cancer-related deaths, where it is associated with a 5-year worldwide survival rate of less than 15% [1,2]
The development and application of drugs that target specific molecules expressed on lung cancer cells has garnered increased attention, and remarkable successes have been reported in several Non-small-cell lung cancer (NSCLC) patient study groups [5,6,7], such as a subset of patients with NSCLC testing positive for activating mutations in the epidermal growth factor receptor (EGFR) gene
EGFR and KRAS are two relevant molecules in NSCLC, and EGFR is targeted by EGFR-tyrosine kinase inhibitors (TKIs)
Summary
Lung cancer is a leading cause of cancer-related deaths, where it is associated with a 5-year worldwide survival rate of less than 15% [1,2]. The development and application of drugs that target specific molecules expressed on lung cancer cells has garnered increased attention, and remarkable successes have been reported in several NSCLC patient study groups [5,6,7], such as a subset of patients with NSCLC testing positive for activating mutations in the epidermal growth factor receptor (EGFR) gene. These cancers exhibit sensitivities to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib or erlotinib, supporting the use of these drugs for effective treatment of NSCLC [5,8]. The utility of EGFR TKIs in these patients highlights the importance of identifying genotype-specific patient subsets to guide the selection of targeted therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
