To assess the prevalence of EML4-ALK rearrangement gene measured by immunohistochemistry in an unselected population-based consecutive cohort of patients with adenocarcinoma of the lung (ACL), and the correlation with smoking history, thyroid transcription factor 1 (TTF1), gender and age.
A total of 253 patients with advanced lung adenocarcinoma received a pemetrexed-based regimen and were classified on the basis of molecular findings as follows: 102 patients (40.3%) with EGFR mutations, 32 patients (12.6%) with EML4-ALK translocation, three patients (1.2%) with KRAS mutations, 19 patients (7.5%) with ROS1 fusion, and 97 patients (38.3%) with quadruple-negative status.
In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib.
It was histologically characterized with micropapillary, lepidic, and papillary subtypes.The mutation rate of EML4-ALK is relatively high in lung adenocarcinoma patients aged<60 years, pathologically characterized with acinar and solid subtypes with mucin secretion.
Serum carcinoembryonic antigen levels before initial treatment are associated with EGFR mutations and EML4- ALK fusion gene in lung adenocarcinoma patients.
Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma.
Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively.
The major driver mutations of lung cancer, EGFR mutations and EML4-ALK fusion, are mainly detected in terminal respiratory unit (TRU)-type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology.
Among the 440 patients with adenocarcinoma of lung screened for this study, 46 (10.4%) harboured the EML4-ALK fusion, 90 (20.4%) harboured an activating EGFR mutation, and all had adenocarcinoma.
In addition, the association between MAGE-A expression and the epithelial growth factor receptor (EGFR) amplification and ALK-EML4 rearrangements of patients with LAC were also analysed.
In this series, 230 resected lung adenocarcinomas from smoker (>100 cigarettes in lifetime) at single center (Shanghai Cancer Center, Shanghai, China) were tested for mutation in EGFR, KRAS, BRAF, HER2, EML4-ALK and PIK3CA.
104 consecutively resected lung adenocarcinomas from 396 non-smoker females (less than 100 cigarettes in a lifetime) at a single institution (Tongji University, Shanghai, China) were analyzed for mutations in EGFR, EML4-ALK, KRAS, HER2, BRAF, and PIK3CA.