EML4-ALK translocation is associated with early onset of disease and other clinicopathological features in Chinese female never-smokers with non-small-cell lung cancer

Ren,Weihong; Zhang,Bo; Ma,Jie; Li,Wencai; Lan,Jianyun; Men,Hui; Zhang,Qinxian

doi:10.3892/ol.2015.3740

EML4-ALK translocation is associated with early onset of disease and other clinicopathological features in Chinese female never-smokers with non-small-cell lung cancer

Authors:
- Weihong Ren
- Bo Zhang
- Jie Ma
- Wencai Li
- Jianyun Lan
- Hui Men
- Qinxian Zhang
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Affiliations: Department of Laboratory Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Jinshui, Zhengzhou, Henan 450000, P.R. China, Department of Pathology, Affiliated Hospital of Academy of Military Medical Sciences, Fengtai, Beijing 100071, P.R. China, The Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Pathology, The First People's Hospital of Yancheng, Yancheng, Jiangsu 224006, P.R. China, Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: September 24, 2015 https://doi.org/10.3892/ol.2015.3740
Pages: 3385-3392
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation is resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, but responds to the ALK‑TKI crizotinib. Characterization of EML4‑ALK translocation may provide invaluable information to facilitate disease diagnosis and improve the outcome of customized treatment. Although the occurrence of EML4‑ALK translocation is likely to be affected by the smoking habits and gender of patients, the translocation has not been characterized extensively in female never‑smokers with NSCLC. Therefore, 280 female never‑smokers that were diagnosed with NSCLC were enrolled in the present study, and characteristics of EML4‑ALK translocation, including the frequency, were determined in these NSCLC patients. EML4‑ALK fusion variants were detected using Multiplex one‑step reverse transcription-polymerase chain reaction and subsequently confirmed by DNA sequencing and Vysis ALK Break Apart fluorescence in situ hybridization analysis. The EML4‑ALK fusion variants were detected in 21 carcinoma tissue specimens, accounting for 7.5% of the enrolled patients. Out of these patients with EML4‑ALK fusion variants, EML4‑ALK fusion variant 1 was identified in 12 patients, indicating that variant 1 is the most common type of EML4‑ALK fusion gene in the present cohort of patients. ALK mRNA was aberrantly expressed in all the tissues with EML4‑ALK translocation, but not in the carcinoma tissues without EML4‑ALK translocation. In addition, the EML4‑ALK translocation was more frequently found in younger patients. The median age of patients with EML4‑ALK translocation was 50.95±2.29 years, which was significantly younger (P<0.01) than the median age of the patients without EML4‑ALK translocation (57.15±0.56). The EML4‑ALK translocation was detected exclusively in undifferentiated tumors that were graded as poorly‑ or moderately‑differentiated carcinomas and suspected to be more malignant compared with well‑differentiated tumors. In summary, the present study found that 7.5% of patients with NSCLC that are female never‑smokers harbor EML4‑ALK translocations, which are associated with the aberrant expression of ALK mRNA, early onset of disease and undifferentiated carcinomas.

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