title: Assessment of epidermal growth factor receptor mutation/copy number and K-ras mutation in esophageal cancer.
abstract: BACKGROUND
  The molecular status of epidermal growth factor receptor (EGFR) in esophageal cancer has not been well elucidated. The purpose of the study was to investigate the prevalence of EGFR and K-ras mutation, and EGFR gene copy number status as well as its association with clinicopathologic characteristics, and also to identify the prognostic value of EGFR gene copy number in esophageal cancer.
  
  
  METHODS
  EGFR mutation in exon 19/exon 21 and K-ras mutation in codon 12/codon 13 were detected by real-time PCR method, while EGFR gene copy number status was analyzed by fluorescent in situ hybridization (FISH). EGFR gene amplification and high polysomy were defined as high EGFR gene copy number status (FISH-positive), and all else were defined as low EGFR gene copy number status (FISH-negative). The relationship between EGFR gene copy number status and clinicpathologic characteristics was analyzed. Kaplan-Meier method and Cox proportional hazards regression model were employed to evaluate the effects of EGFR gene copy number status on the patients' survival.
  
  
  RESULTS
  A total of 57 esophageal squamous cell carcinoma (ESCC) patients and 9 esophageal adenocarcinoma (EADC) patients were enrolled in the study. EGFR mutation was identified in one patient who was diagnosed as ESCC with stage IIIC disease. K-ras mutation was identified in one patient who was diagnosed as EADC. In all, 34 of 66 (51.5%) samples were detected as FISH-positive, which includes 30 ESCC and 4 EADC tumor samples. The correlation analysis showed that FISH-positive was signiﬁcantly associated with the tumor stage (P=0.019) and lymph node metastasis (P=0.005) in esophageal cancer patients, and FISH-positive was also signiﬁcantly associated with the tumor stage (P=0.007) and lymph node metastasis (P=0.008) in ESCC patients. Cox regression analysis showed that high EGFR gene copy number was not a significant predictor of a poor outcome for esophageal cancer patients (P=0.251) or for ESCC patients (P=0.092), but esophageal cancer patients or ESCC patients with low EGFR gene copy number may have longer survival than those with high EGFR gene copy number according to the survival curve trends.
  
  
  CONCLUSIONS
  The results indicated that EGFR or K-ras mutation was rare in esophageal cancer, but high EGFR gene copy number is frequent, and correlated with advanced pathologic stage and more number of the metastatic regional lymph nodes, especially in ESCC. In addition, high EGFR gene copy number is likely to have a deleterious effect on prognosis of esophageal cancer patients or ESCC patients, although no statistical significance was reached in the study.
authors: Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China ;
authors: Kang
authors: K
authors: Guo
authors: Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China ;
authors: Wu-Ping
authors: WP
authors: Wang
authors: Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China ;
authors: Tao
authors: T
authors: Jiang
authors: Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China ;
authors: Ju-Zheng
authors: JZ
authors: Wang
authors: Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China ;
authors: Zhao
authors: Z
authors: Chen
authors: Department of Pathology, Cancer Center of Sun Yat-Sen University, State Key Laboratory in Southern China, Guangzhou 510060, China.
authors: Yong
authors: Y
authors: Li
authors: Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China ;
authors: Yong-An
authors: YA
authors: Zhou
authors: Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China ;
authors: Xiao-Fei
authors: XF
authors: Li
authors: Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China ;
authors: Qiang
authors: Q
authors: Lu
authors: Department of Thoracic Surgery, Cancer Center of Sun Yat-Sen University, State Key Laboratory in Southern China, Guangzhou 510060, China.
authors: Lan-Jun
authors: LJ
authors: Zhang
keywords: EGFR gene copy number; EGFR mutation; K-ras mutation; esophageal cancer; target therapy