Activating mutations within the EGFR kinase domain: a molecular predictor of disease-free survival in resected pulmonary adenocarcinoma.

Full Abstract

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.

Author information

Author/s: Lee, Young Joo (YJ); Park, In Kyu (IK); Park, Moo-Suk (MS); Choi, Hye Jin (HJ); Cho, Byoung Chul (BC); Chung, Kyung Young (KY); Kim, Se Kyu (SK); Chang, Joon (J); Moon, Jin Wook (JW); Kim, Hoguen (H); Choi, Sung Ho (SH); Kim, Joo-Hang (JH);

Affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, CPO Box 8044, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Republic of Korea.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol), published in Germany. (Language: eng)

Reference: 2009-Dec; vol 135 (issue 12) : pp 1647-54

Dates: Created 2009/09/25; Completed 2009/10/08;

PMID: 19517135, status: MEDLINE (last retrieval date: 10/8/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.