PURPOSE: Although epidermal growth factor receptor (EGFR) tyrosine kinase (TK) mutations are highly predictive of response to EGFR TK inhibitors in advanced non-small-cell lung cancer (NSCLC), a prognostic value of EGFR mutations in resected NSCLC has not been established. METHODS: We retrospectively reviewed 117 patients with primary lung adenocarcinoma who underwent surgical resection between 1995 and 2005. Nucleotide sequencing of the kinase domain of EGFR (exons 18-21) was performed using nested PCR amplification of individual exons. RESULTS: Forty-eight patients (41.8%) harbored exon 19 deletion or exon 21 point mutations. EGFR mutations were more frequently found in never-smoker (P = 0.04) or in smaller-sized primary tumor (P = 0.001). A presence of EGFR mutations was significantly associated with longer disease-free survival (DFS) (20.1 vs. 34.4 months in mutated EGFR; P = 0.003). In multivariate analysis of DFS, wild-type EGFR was associated with a higher risk of recurrence, with an adjusted hazard ratio of 1.42 (95% CI, 1.1-2.41, P = 0.04), as compared to mutated EGFR. However, no significant association was observed between EGFR mutations and overall survival (P = 0.39). Isolated brain metastasis as the first recurrence after resection was found more frequently in those patients with tumors bearing EGFR mutations, although the difference was not statistically significant (9 vs. 24% in mutated EGFR, P = 0.15). CONCLUSIONS: Activating mutations within the EGFR TK domain can be used to predict the risk of recurrence in curatively resected pulmonary adenocarcinoma.
Bibliographical noteFunding Information:
Acknowledgment We thank the members of Lung Cancer Clinic Severance Hospital for thoughtful discussion and review of the manuscript. This study was supported by a faculty research grant of Yonsei University College of Medicine for 2008 (6-2008-0107).
All Science Journal Classification (ASJC) codes
- Cancer Research