Identification of EGFR mutations in esophageal cancer.
BACKGROUND
It is well known that the prognosis for esophageal cancer is worse than for other digestive cancers in spite of multimodality treatment, and there is an urgent need to improve this situation. The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, was approved in Japan to treat advanced non-small cell lung cancer patients and several papers have since reported that the successfully treated patients had genetic mutations in EGFR.


OBJECTIVE
The aim of this study was to investigate the existence of EGFR mutations in esophageal cancer cell lines and primary lesions, and also to explore the possibility of treating esophageal cancer using gefitinib.


METHODS
Nineteen esophageal cancer cell lines were cultured and DNA was extracted using an ultracentrifugation method. Fifty cases of primary cancer and corresponding normal tissue samples were obtained and DNA was extracted using the same protocol. Nested PCR and DNA sequencing targeting exons 18, 19, 20 and 21 of EGFR were performed to investigate the presence of mutations in esophageal cancer cell lines and primary tumors.


RESULTS
Three of the 19 cell lines had the same silent mutation at nucleotide 2607, a G-to-A substitution in exon 20. One of the 50 patients had an EGFR mutation in codon 719, resulting in an amino acid substitution from glycine to aspartic acid.


CONCLUSIONS
EGFR mutations in esophageal carcinoma are rare but do exist, and thus gefitinib could be included in esophageal cancer treatment regimens by selecting those patients who possess such mutations.
Sudo
T
T
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan.
Mimori
K
K
Nagahara
H
H
Utsunomiya
T
T
Fujita
H
H
Tanaka
Y
Y
Shirouzu
K
K
Inoue
H
H
Mori
M
M
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D014461:Ultracentrifugation
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D066246:ErbB Receptors