title: Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma.
abstract: BACKGROUND
  The EML4-anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors.
  
  
  METHODS
  We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated.
  
  
  RESULTS
  ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/- assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases.
  
  
  CONCLUSIONS
  Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.
authors: Division of Epidemiology, Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA. yang.ping@mayo.edu
authors: Ping
authors: P
authors: Yang
authors: Kimary
authors: K
authors: Kulig
authors: Jennifer M
authors: JM
authors: Boland
authors: Michele R
authors: MR
authors: Erickson-Johnson
authors: Andre M
authors: AM
authors: Oliveira
authors: Jason
authors: J
authors: Wampfler
authors: Aminah
authors: A
authors: Jatoi
authors: Claude
authors: C
authors: Deschamps
authors: Randolph
authors: R
authors: Marks
authors: Connie
authors: C
authors: Fortner
authors: Shawn
authors: S
authors: Stoddard
authors: Francis
authors: F
authors: Nichols
authors: Julian
authors: J
authors: Molina
authors: Marie-Christine
authors: MC
authors: Aubry
authors: Hui
authors: H
authors: Tang
authors: Eunhee S
authors: ES
authors: Yi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000556:secondary*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012907:Smoking; D055815:Young Adult
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases