EGFR R497K polymorphism is a favorable prognostic factor for advanced lung cancer.
BACKGROUND
It has been reported that the R497K polymorphism of the epidermal growth factor receptor (EGFR) gene has attenuated functions in ligand binding, tyrosine kinase activation, and growth stimulation. On other hand, EGFR gene mutations at kinase domain in non-small cell lung cancer (NSCLC) have been examined for their ability to predict sensitivity to gefitinib or erlotinib.


METHODS
We investigated the EGFR mutations and/or R497K polymorphism statuses in 225 surgically treated NSCLC cases. 192 adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of exon 13 was analyzed by PCR-RFLP method.


RESULTS
EGFR mutations at kinase domain were found from 95 of 225 lung cancer patients. In 86.2% of patients, homo- or heterozygous Lys497 allele was present. No correlation existed between R497K EGFR genotype and clinico-pathological features, such as gender, smoking status, and pathological subtypes.


CONCLUSIONS
EGFR mutation status was not correlated with R497KEGFR genotype of lung cancers. In node-negative patients, R497KEGFR genotype was not correlated with disease outcome. In node-positive patients, however, R497K EGFR was significantly associated with better overall survival. This association was attributable to neo-adjuvant or adjuvant chemotherapy. In 46 total gefitinib treated NSCLC patients, the prognosis was not different between the EGFR wild type (GG) patients and AG+AA patients. R497KEGFR polymorphism might be associated with favorable prognosis of advanced lung cancers and correlated with chemosensitivity.
Sasaki
Hidefumi
H
Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. hisasaki@med.nagoya-cu.ac.jp
Okuda
Katsuhiro
K
Shimizu
Shigeki
S
Takada
Minoru
M
Kawahara
Masaaki
M
Kitahara
Naoto
N
Okumura
Meinoshin
M
Matsumura
Akihide
A
Iuchi
Keiji
K
Kawaguchi
Tomoya
T
Kubo
Akihito
A
Kawano
Osamu
O
Yukiue
Haruhiro
H
Yano
Motoki
M
Fujii
Yoshitaka
Y
D019943:Amino Acid Substitution; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000601:surgery*; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000601:surgery*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis
D004273:DNA, Neoplasm; D066246:ErbB Receptors