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

Authors
 Young Joo Lee  ;  In Kyu Park  ;  Moo-Suk Park  ;  Hye Jin Choi  ;  Byoung Chul Cho  ;  Kyung Young Chung  ;  Se Kyu Kim  ;  Joon Chang  ;  Jin Wook Moon  ;  Hoguen Kim  ;  Sung Ho Choi  ;  Joo-Hang Kim 
Citation
 JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, Vol.135(12) : 1647-1654, 2009 
Journal Title
 JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 
ISSN
 0171-5216 
Issue Date
2009
MeSH
Adenocarcinoma/diagnosis* ; Adenocarcinoma/genetics ; Adenocarcinoma/surgery* ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/surgery ; Cohort Studies ; Disease-Free Survival ; Female ; Genes, erbB-1* ; Humans ; Lung Neoplasms/diagnosis* ; Lung Neoplasms/genetics ; Lung Neoplasms/surgery* ; Male ; Middle Aged ; Mutation*/physiology ; Phosphotransferases/chemistry ; Phosphotransferases/genetics ; Phosphotransferases/metabolism ; Prognosis ; Protein Structure, Tertiary/genetics ; Retrospective Studies
Keywords
Non-small cell lung cancer ; Prognosis ; Epidermal growth factor receptor ; Mutation
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.
Full Text
http://link.springer.com/article/10.1007%2Fs00432-009-0611-7
DOI
10.1007/s00432-009-0611-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Kyu(김세규)
Kim, Joo Hang(김주항)
Kim, Ho Keun(김호근)
Moon, Jin Wook(문진욱)
Park, Moo Suk(박무석) ORCID logo https://orcid.org/0000-0003-0820-7615
Park, In Kyu(박인규)
Chang, Joon(장준) ORCID logo https://orcid.org/0000-0003-4542-6841
Chung, Kyung Young(정경영)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Choi, Hye Jin(최혜진) ORCID logo https://orcid.org/0000-0001-5917-1400
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104558
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