A case of lung adenocarcinoma harboring EGFR mutation and EML4-ALKfusion gene
© Tanaka et al.; licensee BioMed Central Ltd. 2012
Received: 27 March 2012
Accepted: 20 November 2012
Published: 26 November 2012
Lung cancer is the leading cause of cancer-related death worldwide. Epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitor (TKI) is used for the patients with EGFR-mutant lung cancer. Recently, phase III studies in the patients with EGFR-mutant demonstrated that EGFR-TKI monotherapy improved progression-free survival compared with platinum-doublet chemotherapy. The echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion oncogene represents one of the newest molecular targets in non-small cell lung cancer (NSCLC). Patients who harbor EML4-ALK fusions have been associated with a lack of EGFR or KRAS mutations.
We report a 39-year-old patient diagnosed as adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene. We treated this patient with erlotinib as the third line therapy, but no clinical benefit was obtained.
We experienced a rare case with EGFR mutation and EML4-ALK. Any clinical benefit using EGFR-TKI was not obtained in our case. The therapeutic choice for the patients with more than one driver mutations is unclear. We needs further understanding of the lung cancer molecular biology and the biomarker infomation.
KeywordsLung cancer EGFR mutation EML4-ALK Erlotinib
Lung cancer is the leading cause of cancer-related death worldwide. Recent studies on personalized treatment by selecting patients who are likely to respond to a particular therapeutic agent may allow improved treatment efficacy. Patients with non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR) gene have dramatic response to the EGFR- tyrosine kinase inhibitor (EGFR-TKI) [1, 2]. In 2007, the fusion of the anaplastic lymphoma kinase (ALK) with the echinoderm microtubule-associated protein-like 4 (EML4) was identified in NSCLC. EML4-ALK fusion gene arise as a result of an inversion in chromosome 2 that juxtaposed the 5 end of the EML4 gene with the 3 end of the ALK gene. The frequency of the fusion gene is approximately 6.7% in NSCLC . The clinical features of lung cancer that harbors EML4-ALK include light- or never-smokers, younger age, adenocarcinomas with acinar pattern or signet ring adenocarcinoma, and a lack of EGFR or KRAS mutations . Patients who have both mutations are extremely rare.
Patients characteristics and treatment outcomes by EGFR-TKI
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In our case, the characteristics of the patient were young age, light-smoker and acinar pattern adenocaricinoma which showed similarity with the ones of EML4-ALK positive NSCLC. Additionally, PEM therapy showed a good response to our patient, whereas erlotinib therapy did not. In the cases with these both mutations, EML4-ALK gene may play a main role in the oncogenesis for some unknown reasons. Although ALK inhibitor was effective to EML4-ALK positive NSCLC , it was not on the market in Japan at that point. Further experience and the understanding of the lung cancer molecular biology are required for the better treatment of the cases with both EGFR mutation and EML4-ALK fusion gene.
We report a rare case of lung cancer harboring both EGFR mutation and EML4-ALK fusion gene. PEM therapy showed a good response to the patient, whereas erlotinib therapy did not. Oncologists should be aware of the possibility of the multiple mutations.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Epidermal growth factor receptor
Tyrosine kinase inhibitor
Echinoderm microtubule-associated protein-like 4
Anaplastic lymphoma kinase
Non-small cell lung cancer
Trans-bronchial lung biopsy
Cycleave polymerase chain reaction technique
Reverse transcription polymerase chain reaction.
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