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

ABSTRACT

PURPOSE: 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. MATERIALS AND METHODS: A total of 434 primary NSCLC samples were analyzed by fluorescence in situ hybridization (FISH) for ALK GCN. RESULTS: 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. CONCLUSION: 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.