EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) exhibits abnormalities in epidermal growth factor receptor (EGFR) gene. To identify a prognostic marker, the overexpression of EGFR protein, mutations in EGFR and p53 mutations were analyzed in pretreatment biopsy specimens removed from T3-4 and/or M1 LYM ESCC patients who received chemoradiotherapy. A silent mutation comprised of a single nucleotide polymorphism (SNP) at codon 787 of exon 20 of the EGFR gene was found in 19 patients (33%). In multivariate analysis, a significant difference was seen in the overall survival (odds ratio; 2.347, 95% confidence interval; 1.183-4.656, p = 0.015) between patients with and without the EGFR heterozygous genotype. Among the 57 eligible patients, 3-year survival rates was 21%, while in patients with EGFR heterozygous genotype the rate were 0%. However, neither overexpression of EGFR nor p53 mutations was associated with the overall survival. These results suggest that the EGFR SNP at codon 787 of exon 20 determined in pretreatment biopsy specimens may be a clinically useful biomarker for predicting the prognosis of ESCC patients.
Kaneko
Kazuhiro
K
Division of Digestive Endoscopy/Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, 277-8577, Japan. kkaneko@east.ncc.go.jp
Kumekawa
Yosuke
Y
Makino
Reiko
R
Nozawa
Hisako
H
Hirayama
Yuichi
Y
Kogo
Mari
M
Konishi
Kazuo
K
Katagiri
Atsushi
A
Kubota
Yutaro
Y
Muramoto
Takashi
T
Kushima
Miki
M
Ohmori
Tohru
T
Oyama
Tsunehiro
T
Kagawa
Norio
N
Ohtsu
Atsushi
A
Imawari
Michio
M
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D005455:Fluorescent Antibody Technique; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011878:Radiotherapy / Q000379:methods; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D002945:Cisplatin; D005472:Fluorouracil