J Lung Cancer.  2011 Dec;10(2):87-93. 10.6058/jlc.2011.10.2.87.

Clinicopathologic Implications of ALK Gene Copy Number Gain in Non-small Cell Lung Cancer

  • 1Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. chungjh@snu.ac.kr
  • 2Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
  • 3Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
  • 4Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.


The anaplastic lymphoma kinase (ALK) gene is a potential molecular target in non-small cell lung carcinoma (NSCLC). The clinicopathologic implication of a change in the ALK gene copy number (GCN) is unclear.
A total of 434 primary NSCLC samples were analyzed by fluorescence in situ hybridization (FISH) for ALK GCN.
Ninety-six cases (22.1%) showed ALK GCN gain with amplification in 16 (3.7%) cases. The cases with ALK GCN gain consisted of 47 adenocarcinomas (49.0%), 41 squamous cell carcinomas (42.7%), 5 adenosquamous carcinomas (5.2%) and 3 other NSCLCs (3.1%). ALK gene amplification was identified in 7 adenocarcinomas (43.7%) and 9 squamous cell carcinomas (56.3%). There was no significant difference between ALK GCN gain/amplification and histologic subtypes. Univariate survival analysis revealed that patients with ALK GCN gain/amplification showed shorter progression-free survival durations and decreased overall survival rates (p<0.001). However, multivariate analysis proved that ALK GCN gain/amplification is not an independent prognostic factor for progression-free survival or overall survival.
ALK GCN gain is frequently identified in NSCLCs and the incidence is similar among histologic subtypes. Although ALK GCN gain/amplification is not an independent prognostic marker, it is associated with tumor progression in NSCLC.


ALK; Copy number gain; Gene amplification; Non-small cell lung carcinoma

MeSH Terms

Carcinoma, Adenosquamous
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Disease-Free Survival
Gene Amplification
Gene Dosage
In Situ Hybridization
Multivariate Analysis
Receptor Protein-Tyrosine Kinases
Survival Rate
Receptor Protein-Tyrosine Kinases


  • Fig. 1. ALK gene status by fluorescence in situ hybridization (FISH) (×1,000). (A) ALK gene rearrangement (break-apart pattern). (B) ALK gene copy number gain. (C) ALK gene amplification. (D) ALK wild type.

  • Fig. 2. ALK gene copy number gain/amplification showed significantly shorter progression-free survival (A) and overall-survival (B).


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