Identification of exon 19 and 21 mutations of EGFR gene in Chinese patients with esophageal squamous cell carcinoma

Yong Cui,Xu Zhang,Baojian Zhao,Mingliang Liu,Dong Chang,Changjin Lin,Min Gong

doi:10.1186/1477-7819-11-266

Abstract

BackgroundAlthough epidermal growth factor receptor (EGFR) inhibitor treatment showed modest response in several clinical trials in esophageal squamous cell carcinoma (ESCC) patients, it has been reported that the frequency of EGFR mutations varied largely. The aim of this study was to investigate the existence of EGFR mutations in Chinese esophageal squamous cell carcinomas.MethodsFormalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 127 randomly selected Chinese patients with ESCC. The most common EGFR mutations, including in-frame deletions in exon 19 and base substitutions in exon 21, were detected by denaturing high performance liquid chromatography (DHPLC) and direct sequencing simultaneously. K-RAS mutations in codons 12 and 13 were detected by direct sequencing.ResultsIn this study, L858R missense mutations of the EGFR gene were found in 8 out of 127 patients (6.3%) by DHPLC but no mutation was observed by direct sequencing. In addition, K-RAS mutation was detected in 2 out of 127 (1.6%) patients by direct sequencing.ConclusionsThe incidence of EGFR mutations was relatively high using DHPLC method but no mutation with direct sequencing in Chinese ESCC patients.

Highlights

Epidermal growth factor receptor (EGFR) inhibitor treatment showed modest response in several clinical trials in esophageal squamous cell carcinoma (ESCC) patients, it has been reported that the frequency of epidermal growth factor receptor (EGFR) mutations varied largely
One of the most promising targets is the inhibition of the epidermal growth factor receptor (EGFR) by monoclonal antibodies or small molecule tyrosine kinase inhibitors
Studies have showed that the kinase domain mutations of the EGFR gene in the non-small-cell lung cancer (NSCLC) tissues correlate with clinical responses to gefitinib

Summary

Introduction

Epidermal growth factor receptor (EGFR) inhibitor treatment showed modest response in several clinical trials in esophageal squamous cell carcinoma (ESCC) patients, it has been reported that the frequency of EGFR mutations varied largely. Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer and is one of the most aggressive malignant tumors in China [1]. One of the most promising targets is the inhibition of the epidermal growth factor receptor (EGFR) by monoclonal antibodies (for example, cetuximab, panitumumab) or small molecule tyrosine kinase inhibitors (for example, erlotinib, gefitinib). Studies have showed that the kinase domain mutations of the EGFR gene in the non-small-cell lung cancer (NSCLC) tissues correlate with clinical responses to gefitinib. K-RAS mutations are associated with intrinsic tyrosine kinase inhibitor (TKI) resistance in patients with lung cancer [7,8]. Molecular diagnosis of these mutations is increasingly important in making therapeutic decisions

Objectives

Methods

Results

Conclusion