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EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous cell carcinoma
Kazuhiro Kaneko1,Yosuke Kumekawa1,Reiko Makino1,Hisako Nozawa1,Yuichi Hirayama1,Mari Kogo1,Kazuo Konishi1,Atsushi Katagiri1,Yutaro Kubota1,Takashi Muramoto1,Miki Kushima1,Tohru Ohmori1,Tsunehiro Oyama1,Norio Kagawa1,Atsushi Ohtsu1,Michio Imawari1
1
Division of Digestive Endoscopy/Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, 277-8577, Japan. kkaneko@east.ncc.go.jp
DOI: 10.2741/3607 Volume 15 Issue 1, pp.65-72
Published: 01 January 2010
(This article belongs to the Special Issue Gene regulation and structure-function of P450 Cold stress response)
Abstract

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.

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Kazuhiro Kaneko, Yosuke Kumekawa, Reiko Makino, Hisako Nozawa, Yuichi Hirayama, Mari Kogo, Kazuo Konishi, Atsushi Katagiri, Yutaro Kubota, Takashi Muramoto, Miki Kushima, Tohru Ohmori, Tsunehiro Oyama, Norio Kagawa, Atsushi Ohtsu, Michio Imawari. EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous cell carcinoma. Frontiers in Bioscience-Landmark. 2010. 15(1); 65-72.