Format

Send to

Choose Destination
Oncol Lett. 2015 Dec;10(6):3385-3392. Epub 2015 Sep 24.

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.

Author information

1
Department of Laboratory Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Jinshui, Zhengzhou, Henan 450000, P.R. China; Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
2
Department of Pathology, Affiliated Hospital of Academy of Military Medical Sciences, Fengtai, Beijing 100071, P.R. China.
3
The Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
4
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
5
Department of Pathology, The First People's Hospital of Yancheng, Yancheng, Jiangsu 224006, P.R. China.
6
Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

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.

KEYWORDS:

EML4-ALK translocation; female; lung cancer; never smokers

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center