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

Young Joo Lee, In Kyu Park, Moo Suk Park, Hye Jin Choi, ByoungChul Cho, Kyung Young Chung, Se Kyu Kim, Joon Chang, Jin Wook Moon, Hoguen Kim, Sung Ho Choi, Joo Hang Kim

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1647-1654
Number of pages8
JournalJournal of cancer research and clinical oncology
Volume135
Issue number12
DOIs
Publication statusPublished - 2009 Jan 1

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Epidermal Growth Factor Receptor
Disease-Free Survival
Mutation
Exons
Protein-Tyrosine Kinases
Recurrence
Non-Small Cell Lung Carcinoma
Adenocarcinoma of lung
Point Mutation
Neoplasms
Multivariate Analysis
Nucleotides
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lee, Young Joo ; Park, In Kyu ; Park, Moo Suk ; Choi, Hye Jin ; Cho, ByoungChul ; Chung, Kyung Young ; Kim, Se Kyu ; Chang, Joon ; Moon, Jin Wook ; Kim, Hoguen ; Choi, Sung Ho ; Kim, Joo Hang. / Activating mutations within the EGFR kinase domain : a molecular predictor of disease-free survival in resected pulmonary adenocarcinoma. In: Journal of cancer research and clinical oncology. 2009 ; Vol. 135, No. 12. pp. 1647-1654.
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title = "Activating mutations within the EGFR kinase domain: a molecular predictor of disease-free survival in resected pulmonary adenocarcinoma.",
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.",
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Activating mutations within the EGFR kinase domain : a molecular predictor of disease-free survival in resected pulmonary adenocarcinoma. / Lee, Young Joo; Park, In Kyu; Park, Moo Suk; Choi, Hye Jin; Cho, ByoungChul; Chung, Kyung Young; Kim, Se Kyu; Chang, Joon; Moon, Jin Wook; Kim, Hoguen; Choi, Sung Ho; Kim, Joo Hang.

In: Journal of cancer research and clinical oncology, Vol. 135, No. 12, 01.01.2009, p. 1647-1654.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Activating mutations within the EGFR kinase domain

T2 - a molecular predictor of disease-free survival in resected pulmonary adenocarcinoma.

AU - Lee, Young Joo

AU - Park, In Kyu

AU - Park, Moo Suk

AU - Choi, Hye Jin

AU - Cho, ByoungChul

AU - Chung, Kyung Young

AU - Kim, Se Kyu

AU - Chang, Joon

AU - Moon, Jin Wook

AU - Kim, Hoguen

AU - Choi, Sung Ho

AU - Kim, Joo Hang

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

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