title: EML4-ALK rearrangement and its clinical significance in Chinese patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  To identify the clinicopathological characteristics and clinical outcomes of Chinese patients with non-small cell lung cancer (NSCLC) and to investigate possible associations of NSCLC with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutations.
  
  
  METHODS
  Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at the Peking University Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization and confirmed by immunohistochemistry. EGFR mutations were determined using denaturing high-performance liquid chromatography.
  
  
  RESULTS
  The incidence of EML4-ALK was 9.7% (11/113). Patients with EML4-ALK were more likely to present the EGFR wild type (WT; p = 0.033). Response to EGFR-tyrosine kinase inhibitor (TKI) was similar between patients with EML4-ALK rearrangement and EGFR mutation (33.3 vs. 46.9%, p = 0.451), but progression-free survival (PFS) was inferior compared to those with EGFR mutation (2.1 vs. 8.8 months, p = 0.032), and similar to patients with WT/nonrearrangement (2.1 vs. 2.2 months, p = 0.696; and general p = 0.023 between the three cohorts). Moreover, 2 patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared to patients with single EML4-ALK rearrangement.
  
  
  CONCLUSIONS
  Patients with EML4-ALK conferred similar objective response rates after EGFR-TKI although inferior PFS compared to those with EGFR mutation. Coexistence of EML4-ALK and EGFR mutation might represent a separate NSCLC genotype.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Wang
authors.forename: Xuchao
authors.initials: X
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Minglei
authors.initials: M
authors.lastname: Zhuo
authors.forename: Tongtong
authors.initials: T
authors.lastname: An
authors.forename: Jianchun
authors.initials: J
authors.lastname: Duan
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Meina
authors.initials: M
authors.lastname: Wu
authors.forename: Shuhang
authors.initials: S
authors.lastname: Wang
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yilong
authors.initials: Y
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002681:China; D002851:Chromatography, High Pressure Liquid; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017671:Platinum Compounds / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D017671:Platinum Compounds; D066246:ErbB Receptors