[Frontiers in Bioscience 15, 65-72, January 1, 2010]

EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous cell carcinoma

Kazuhiro Kaneko1,2, Yosuke Kumekawa2, Reiko Makino3, Hisako Nozawa2, Yuichi Hirayama2,4, Mari Kogo5, Kazuo Konishi2, Atsushi Katagiri2, Yutaro Kubota2, Takashi Muramoto2, Miki Kushima4, Tohru Ohmori6, Tsunehiro Oyama7, Norio Kagawa8, Atsushi Ohtsu1, Michio Imawari2

1 Division of Digestive Endoscopy/Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, 277-8577, Japan,2 Department of Gastroenterology, Showa University School of Medicine, Tokyo, 142-8666, Japan, 3 Clinical Research Laboratory, Showa University School of Medicine, Tokyo, 142-8666, Japan, 4 Division of Pathology, Showa University School of Medicine, Tokyo, 142-8666, Japan, 5 Promotion Center of Pharmaceutical Education, School of Pharmaceutical Sciences, Showa University, Tokyo, 142-8666, Japan,6 Institute of Molecular Oncology, Showa University School of Medicine, Tokyo, 142-8666, Japan,7 Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan, 8 Global COE, Nagoya University School of Medicine, Nagoya, 466-8550, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Patients
3.2. Treatment schedule
3.3. Evaluation of response to chemoradiotherapy
3.4. Sample collection
3.5. DNA extraction
3.6. Analysis of the EGFR and p53 genes
3.7. Immunofluorescence
3.8. Statistical Analysis
4. Results
4.1. Patient characteristics
4.2. EGFR single nucleotide polymorphism
4.3. Immunofluorescent analysis of EGFR
4.4. p53 mutations in esophageal carcinoma
4.5. Clinical response and survival
5. Discussion
6. Acknowledgements
7. References

1. 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.