title: Serum HER2 as a predictive biomarker for tissue HER2 status and prognosis in patients with gastric cancer.
abstract: OBJECTIVE
  To investigate the association between serum human epidermal growth factor receptor 2 (HER2) extracellular domain (ECD) and tissue HER2 status, and the prognostic value of serum HER2 ECD in patients with gastric cancer.
  
  
  METHODS
  A total of 239 patients with gastric cancer were enrolled from December 2012 to June 2013. Serum HER2 ECD was determined by chemiluminescent assay, and tissue HER2 status was evaluated by immunohistochemistry and fluorescencein situhybridization assay. A receiver operating characteristic (ROC) curve was plotted to identify the optimal cut-off value for serum HER2 ECD assay for predicting survival in gastric cancer patients.
  
  
  RESULTS
  Serum HER2 ECD was significantly correlated with tissue HER2 status (P< 0.001), tumor size (P< 0.001), and intestinal type of gastric cancer (P= 0.021). Serum HER2 ECD levels differed significantly between patients with HER2-positive tissue expression and those with HER2-negative tissue expression. ROC analysis yielded an area under the curve value of 0.79 (95%CI: 0.71-0.87,P< 0.001), with a sensitivity and specificity of 0.54 (95%CI: 0.37-0.70) and 0.93 (95%CI: 0.88-0.96), respectively. With a cut-off value of 24.75 ng/mL, high serum HER2 ECD had a negative impact on overall survival of the patients (HR: 1.93, 95%CI: 1.32-4.38,P= 0.006).
  
  
  CONCLUSIONS
  Serum HER2 ECD could be a highly specific surrogate biomarker for tissue HER2 status in gastric cancer. Optimal cut-off criteria for predicting survival should be established.
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Shi
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Huang
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Ke-Cheng
authors.initials: KC
authors.lastname: Zhang
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Hong-Qing
authors.initials: HQ
authors.lastname: Xi
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Cui
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Guo-Xiao
authors.initials: GX
authors.lastname: Liu
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Liang
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.affiliation: Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D000072417:Protein Domains; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D012189:Retrospective Studies; D012698:Serologic Tests / Q000379:methods; D013274:Stomach Neoplasms / Q000097:blood* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Gastric cancer; Prognosis; Serum HER2 extracellular domain; Tissue HER2 status