title: Expression of amphiregulin predicts poor outcome in patients with pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  The validation of novel diagnostic, prognostic and predictive biomarkers in cancer is crucial for optimizing the choice and efficacy of personalized therapies. The aim of this study was to determine the epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRvIII) and amphiregulin (AREG) protein expression levels and to evaluate the prognostic significance of EGFR, EGFRvIII and AREG in pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  The EGFR, EGFRvIII and AREG protein levels in PDAC (n = 92) were examined by using immunohistochemistry. The associations between EGFRvIII expression, AREG expression, AREG/EGFR co-expression and clinicopathological factors were assessed, the correlation between AREG and EGFR expression was analyzed and the survival analyses were performed.
  
  
  RESULTS
  Among the lesions of PDAC, 12 (13 %) stained positive for EGFRvIII, 49 (53.3 %) stained positive for AREG and 22(23.9 %) stained double positive for AREG/EGFR. The relationships between each protein expression level and the clinicopathologic factors were examined, only AREG/EGFR co-expression was significantly related to tumor differentiation (P = 0.032). The correlation between AREG and EGFR expression was statistically insignificant (P = 0.709). Univariate survival analysis proved that high tumor-node-metastasis (TNM) stage, poor tumor differentiation and AREG expression were significant poor prognostic factors for disease-free survival (DFS) and overall survival (OS). By multivariate survival analysis, tumor differentiation was an independent poor prognostic factor for DFS (HR = 1.785, P < 0.05), whereas high TNM stage (HR = 2.25, P < 0.05), poor tumor differentiation (HR = 2.125, P < 0.01), positive resection margins (HR = 1.84, P < 0.05), and AREG expression (HR = 1.822, P < 0.05) were all independent poor prognostic factors for OS.
  
  
  CONCLUSIONS
  In conclusion, our data indicate that AREG expression is an important prognostic biomarker in PDAC .
authors.affiliation: Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People's Republic of China.
authors.forename: Huanwen
authors.initials: H
authors.lastname: Wu
authors.affiliation: Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People's Republic of China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Lu
authors.affiliation: Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People's Republic of China.
authors.forename: Huanli
authors.initials: H
authors.lastname: Duan
authors.affiliation: Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People's Republic of China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People's Republic of China. liangzhiyong1220@yahoo.com.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D011379:Prognosis
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; C410723:epidermal growth factor receptor VIII; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: AREG; EGFR; EGFRvIII; Pancreatic ductal adenocarcinoma