Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer.
To evaluate the epidermal growth factor receptor (EGFR) protein expression, gene mutations and amplification as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib, we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR amplification and EGFR protein expression statuses in 27 surgically treated non-small-cell lung cancer (NSCLC) cases. These patients experienced relapse after surgery and received gefitinib 250 mg/day. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR mutations were found from 15/27 lung cancer patients. EGFR mutation status was significantly correlated with better prognosis (log-rank test P=0.0023). Smoking status (never smoker vs. smoker, P=0.0032), and pathological subtypes (adenocarcinoma vs. non-adenocarcinoma, P=0.0011), but not EGFR amplification (P=0.1278), were correlated with survival of lung cancers. EGFR IHC results were correlated with FISH results (P=0.0125), but not correlated with prognosis (P=0.7921). Thus, the EGFR gene amplification or protein expression is not a predictor of gefitinib efficacy in Japanese patients with NSCLC. We have also evaluated the EGFR mutation status and clinico-pathological features for 27 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. The EGFR mutation status, especially exon19 mutation was correlated with good response to gefitinib than exon 21 point mutation.
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
Endo
Katsuhiko
K
Okuda
Katsuhiro
K
Kawano
Osamu
O
Kitahara
Naoto
N
Tanaka
Hisaichi
H
Matsumura
Akihide
A
Iuchi
Keiji
K
Takada
Minoru
M
Kawahara
Masaaki
M
Kawaguchi
Tomoya
T
Yukiue
Haruhiro
H
Yokoyama
Tomoki
T
Yano
Motoki
M
Fujii
Yoshitaka
Y
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D005784:Gene Amplification; D018628:Gene Dosage; D018773:Genes, erbB-1; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib