Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma

Lung Cancer. 2014 Mar;83(3):389-95. doi: 10.1016/j.lungcan.2014.01.003. Epub 2014 Jan 14.


Objectives: The aim of this study is to evaluate the prevalence and prognostic significance of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangement in never-smokers with surgically resected lung adenocarcinoma.

Methods: We retrospectively analyzed 162 consecutive never-smokers who underwent curative resection for stage IB to IIIA lung adenocarcinoma at a single institution. We concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes, and investigated ALK rearrangements by fluorescence in situ hybridization assay. ROS1 rearrangement was also determined in all triple (EGFR/KRAS/ALK)-negative tumors.

Results: Of 162 never smokers with lung adenocarcinoma, 14 (8.6%) and 5 (3.1%) had ALK and ROS1 rearrangements, respectively. Nineteen of the 74 (25.7%) EGFR and KRAS mutation-negative patients were fusion-positive (ALK or ROS1 fusion). Fusion-positive patients tended to have shorter median disease-free survival (DFS) than fusion-negative patients (28.0 vs. 33.9 months; p=0.128). In multivariate analysis, fusion-positive patients had significantly poorer DFS than fusion-negative patients after adjustment for age, sex, T stage, N stage, and adjuvant chemotherapy use (p=0.022; hazard ratio, 2.11; 95% confidence interval, 1.19-4.30). The first recurrence sites were not significantly different between fusion-positive and fusion-negative patients in this study.

Conclusion: This study shows significantly poorer DFS of ALK or ROS1 fusion-positive lung adenocarcinoma in never-smokers after curative surgery.

Keywords: Anaplastic lymphoma kinase; C-ros oncogene 1; Lung adenocarcinoma; Never-smokers; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality*
  • Anaplastic Lymphoma Kinase
  • DNA Mutational Analysis
  • ErbB Receptors / genetics
  • Gene Rearrangement / genetics
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Mutation / genetics
  • Neoplasm Staging
  • Pneumonectomy
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Recurrence
  • Retrospective Studies
  • Smoking
  • Survival Analysis
  • ras Proteins / genetics


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • ALK protein, human
  • Alk protein, rat
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins