Activating mutations within the EGFR kinase domain: a molecular predictor of disease-free survival in resected pulmonary adenocarcinoma.
OBJECTIVE
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.
Lee
Young Joo
YJ
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.
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
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D017434:Protein Structure, Tertiary / Q000235:genetics; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D010770:Phosphotransferases