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

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TECHNICAL INNOVATIONS

WORLD JOURNAL OF SURGICAL ONCOLOGY

Open Access

Identification of exon 19 and 21 mutations of EGFR gene in Chinese patients with esophageal squamous cell carcinoma Yong Cui1, Dong Chang1, Mingliang Liu1, Changjin Lin1, Baojian Zhao2, Xu Zhang2 and Min Gong1*

Abstract Background: Although 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. Methods: Formalin-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. Results: In 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. Conclusions: The incidence of EGFR mutations was relatively high using DHPLC method but no mutation with direct sequencing in Chinese ESCC patients. Keywords: Epidermal growth factor receptor, Esophageal squamous cell carcinoma, Denaturing high performance liquid chromatography

Background 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]. Despite remarkable advances in multimodal therapies, patient prognosis remains poor, even for those whose carcinomas have been completely resected [2,3]. The limited improvement in treatment outcomes by conventional therapies urged us to seek innovative strategies for treating ESCC, especially those that are molecularly targeted. 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) * Correspondence: [email protected] 1 Department of Thoracic and Cardiovascular Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China Full list of author information is available at the end of the article

[4,5]. The EGFR is a member of the ErbB receptor tyrosine kinase family and plays an important role in cell cycle progression, angiogenesis, metastasis, and protection from apoptosis. 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. Most of the mutations were located in exons 19 and 21 of the EGFR gene incl