title: EML4-ALKtranslocation is associated with early onset of disease and other clinicopathological features in Chinese female never-smokers with non-small-cell lung cancer.
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 ofEML4-ALKtranslocation, 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 fluorescencein situhybridization 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 withEML4-ALKfusion 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.
authors.affiliation: 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.
authors.forename: Weihong
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Pathology, Affiliated Hospital of Academy of Military Medical Sciences, Fengtai, Beijing 100071, P.R. China.
authors.forename: B O
authors.initials: BO
authors.lastname: Zhang
authors.affiliation: The Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Wencai
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology, The First People's Hospital of Yancheng, Yancheng, Jiangsu 224006, P.R. China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Lan
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Men
authors.affiliation: Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Qinxian
authors.initials: Q
authors.lastname: Zhang
keywords: EML4-ALK translocation; female; lung cancer; never smokers