title: Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase-positive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors.
abstract: BACKGROUND
  The purpose of this study was to analyze the clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase (ALK)-positive advanced pulmonary adenocarcinoma and to devise an effective screening strategy to identify such patients.
  
  
  METHODS
  We screened advanced pulmonary adenocarcinoma patients to identify ALK-positive cases. The presence of ALK rearrangements was confirmed by fluorescence in situ hybridization.
  
  
  RESULTS
  Of the 221 screened patients, 45 demonstrated ALK rearrangements, and these individuals were younger than the ALK-negative patients (p < 0.001). The proportion of never smokers and light smokers was found not to differ according to the ALK status (p = 0.537). Epidermal growth factor receptor (EGFR) mutations and ALK rearrangements were found to be mutually exclusive. Thyroid-transcription factor-1 (TTF-1) expression was observed in all ALK-positive tumors for which immunohistochemistry data were available. The objective response rate and progression-free survival to first-line platinum-based chemotherapy showed no significant differences between ALK-positive and ALK-negative patients. On the other hand, no patient with ALK-positive tumors achieved objective tumor responses to EGFR tyrosine kinase inhibitors (TKIs). ALK rearrangements were not found among individuals who had EGFR mutations, an objective response to a previous EGFR TKI treatment or TTF-1-negative tumors.
  
  
  CONCLUSIONS
  The clinical outcomes of platinum-based chemotherapy were found not to differ according to the ALK status. Both smokers and never/light smokers should be candidates for ALK screening. We suggest that the exclusion of patients with activating EGFR mutations, an objective response to previous EGFR TKIs, or TTF-1-negative tumors from ALK screening could be an effective enrichment strategy for ALK-positive cases.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Koh
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Kim
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
authors.forename: Woo-Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D018279:Carcinoma, Signet Ring Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate; D014157:Transcription Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; C504003:TTF1 protein, human; D014157:Transcription Factors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases