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Background Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane.The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC,and help to identify patients who may benefit from EGFR targeted therapies.Methods Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC,16 cases of squamous epithelial atypical hyperplasia,and 11 cases of normal esophageal tissue.Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC,eight cases of squamous epithelial atypical hyperplasia,and eight samples of normal esophageal tissue.Results The IHC-positive rates of EGFR in 105 cases of ESCC,16 cases of squamous epithelial atypical hyperplasia,and 11 normal esophageal tissues were 97％ (102/105),44％ (7/16),and 18％ (2/11) respectively.The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P ＜0.05).Among the 105 cases of ESCC,overexpression of EGFR was found in 90 cases (86％),of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+.In ESCC,the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P＜0.05),but not with other parameters.The FISH-positive rates of EGFR in 80 cases of ESCC,the eight cases of squamous epithelial atypical hyperplasia,and eight samples of normal esophageal tissue were 31.3％ (25/80),0 (0/8) and 0 (0/8) respectively.In ESCC,EGFR gene amplification was found in 17 (21％) cases,high polysomy in 8 (10％) cases,disomy in 34 cases,low trisomy in 17 cases,and high trisomy in four cases.EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P ＜0.05).EGFR FISH-positive was significantly associated with overexpression of EGFR.Conclusion Protein overexpression and/or increased gene copy number of EGFR is common in ESCC,and EGFR targeted therapy may be appropriate for ESCC patients.