title: Amphiregulin is a promising prognostic marker for liver metastases of colorectal cancer.
abstract: OBJECTIVE
  Aberrant activation of epidermal growth factor receptors (EGFR/HER1) by ligand stimulation or heterodimerization with human epidermal growth factor 2 (HER2) is considered to play an important role in the development of colorectal carcinoma. Amphiregulin (AR) is a ligand of EGFR that might be related to the development and progression of gastrointestinal tumors. The aim of this study was to determine the AR, EGFR, and HER2 protein expression levels and to evaluate their prognostic relevance to the clinical course of colorectal cancer.
  
  
  METHODS
  The AR, EGFR, and HER2 protein levels in primary tumors of colorectal cancer (n = 106) were examined using immunohistochemistry. Metastatic sites in liver specimens (n = 16) were also analyzed in the same manner.
  
  
  RESULTS
  Thirteen (81.6%) metastatic lesions of the liver stained positive for AR. Among the primary lesions of colorectal cancer, 58 (54.7%) stained positive for AR, 13 (12.3%) stained positive for EGFR, and 5 (4.7%) stained positive for HER2. When the relationships between each protein expression level and the clinicopathologic factors were examined, only the AR expression level was significantly related to liver metastasis (P = 0.0296). A multivariate analysis of liver metastasis proved that AR expression was an independent prognostic factor of liver metastasis from colorectal cancer (P = 0.0217).
  
  
  CONCLUSIONS
  AR expression in primary lesions of colorectal cancer is an important predictive marker of liver metastasis.
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Yamada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Momiyama
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Ota
authors.forename: Syoichi
authors.initials: S
authors.lastname: Fujii
authors.forename: Kuniya
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shinji
authors.initials: S
authors.lastname: Togo
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D066255:EGF Family of Proteins; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D014408:Biomarkers, Tumor; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins