A correlation between EGFR gene mutation status and bronchioloalveolar carcinoma features in Japanese patients with adenocarcinoma.
BACKGROUND
The presence of epidermal growth factor receptor (EGFR) mutations in gefitinib-naive lung cancer patients has been reported to be higher in females, in non-smokers, in Japanese, and in adenocarcinoma patients, especially in bronchioloalveolar carcinoma (BAC). To further investigate the prevalence of EGFR mutations in relation to pathological factors, we evaluated EGFR mutations in series of Japanese adenocarcinoma patients who had never been treated with gefitinib.


METHODS
In the previous studies, we examined mutation status in the tyrosine kinase domain of EGFR, exon18 through exon21, in 112 primary lung adenocarcinoma samples. Using these data, adenocarcinomas were histologically classified according to the presence or absence of bronchioloalveolar components.


RESULTS
Among 112 patients, 48 had adenocarcinoma with BAC components. Those with adenocarcinomas with BAC components had higher frequency of EGFR mutation (28/48, 58%) than those with non-BAC adenocarcinoma (24/64, 37%, P = 0.036). Male patients had the same trend; 12/23 (52%) male patients with adenocarcinoma with BAC components and 10/47 (21%) of those with non-BAC adenocarcinoma had EGFR mutation (P = 0.0135) but there was no correlation between the EGFR mutation status and with/without BAC components in 42 female patients (P = 0.30). Among 11 male non-smokers, patients with adenocarcinoma with BAC components had a tendency to have EGFR mutation more frequently than those with non-BAC adenocarcinoma (P = 0.061). In clear contrast, the frequency of EGFR mutation did not differ significantly between male smoker patients with adenocarcinoma with BAC components and those with non-BAC. Among patients with adenocarcinoma with BAC components, those with adenocarcinoma with EGFR gene mutation had a significantly better 5 year survival than those with adenocarcinoma with wild-type (85.7 versus 46.0%, P = 0.0017).


CONCLUSIONS
Adenocarcinomas with BAC components in male non-smokers seem to predict the presence of EGFR mutation. Half of female adenocarcinoma patients with EGFR mutation exhibit adenocarcinomas with non-BAC suggesting a different behavior from those in males. The prognosis of patients with adenocarcinoma with BAC components with EGFR gene mutation is predicted to be better than that of patients with adenocarcinoma with BAC components with wild-type EGFR gene.
Haneda
Hiroshi
H
Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.
Sasaki
Hidefumi
H
Lindeman
Neal
N
Kawano
Osamu
O
Endo
Katsuhiko
K
Suzuki
Eriko
E
Shimizu
Shigeki
S
Yukiue
Haruhiro
H
Kobayashi
Yoshihiro
Y
Yano
Motoki
M
Fujii
Yoshitaka
Y
D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000145:classification / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D012189:Retrospective Studies
D066246:ErbB Receptors