title: Amphiregulin and Epiregulin mRNA expression in primary colorectal cancer and corresponding liver metastases.
abstract: BACKGROUND
  Amphiregulin (AREG) and Epiregulin (EREG), ligands of EGFR, are reported to be predictive biomarkers of colorectal cancer patients treated with Cetuximab, an anti-EGFR antibody. The purpose of this study is to determine the correlation of AREG and EREG expression between primary colorectal cancer and corresponding liver metastases.
  
  
  METHODS
  One hundred twenty colorectal cancer patients with liver metastases (100 with synchronous metastases, 20 with metachronous) were evaluated. No patients had ever received anti-EGFR antibody agents. AREG and EREG mRNA expression from both the primary tumor and liver metastases were measured using real-time RT-PCR. KRAS codon 12, 13 mutation status was analyzed by direct sequencing.
  
  
  RESULTS
  Modest, but significant, correlations were observed between primary tumor and corresponding liver metastases in both AREG mRNA expression (Rs = 0.54, p < 0.0001) and EREG mRNA expression (Rs = 0.58, p < 0.0001). AREG and EREG mRNA expression was strongly correlated in both the primary tumor (Rs = 0.81, p < 0.0001) and the liver metastases (Rs = 0.87, p < 0.0001). No significant survival difference was observed between low and high AREG or EREG patients when all 120 patients were analyzed. However, when divided by KRAS status, KRAS wild-type patients with low EREG mRNA levels in the primary site showed significantly better overall survival rates than those with high levels (p = 0.018). In multivariate analysis, low EREG expression was significantly associated with better overall survival (p = 0.006).
  
  
  CONCLUSIONS
  AREG and EREG expression showed a modest correlation between primary tumor and liver metastases. As EREG mRNA expression was associated with decreased survival, it is appeared to be a useful prognostic marker in KRAS wild-type patients who never received anti-EGFR therapy.
authors.affiliation: Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjukuku, Tokyo, Japan. Kuramochi@chemo.twmu.ac.jp
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kuramochi
authors.forename: Go
authors.initials: G
authors.lastname: Nakajima
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakamura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000235:genetics*; D066260:Epiregulin; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D014408:Biomarkers, Tumor; D066255:EGF Family of Proteins; C587880:EREG protein, human; D066260:Epiregulin; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins