Evaluation of extracellular signal regulated kinase expression and its relation to treatment of hepatocellular carcinoma

J Am Coll Surg. 2005 Sep;201(3):405-11. doi: 10.1016/j.jamcollsurg.2005.05.015.


Background: The aim of this study was to evaluate hepatocellular carcinoma (HCC) using a combination of extracellular signal regulated kinase (ERK) and other markers related to hepatocyte growth factor (HGF) in tumor tissue.

Study design: Using specimens from 30 hepatocellular carcinoma patients operated on in our department from 2002 to 2003, we evaluated expression levels of HGF, c-Met, ERK, and cyclin D1 by Western blot.

Results: Expression levels of ERK and cyclin D1 proteins were significantly higher in patients with less well-differentiated type tumors by histologic examination or the presence of intrahepatic metastasis (IM). ERK expression in tumor tissue significantly correlated with both tumor size (p=0.0017, R(2)=0.355) and serum levels of HGF (p=0.0247, R(2)=0.218). Nontumor tissue level of cyclin D1 was significantly higher in patients with poor liver function (p=0.047). In patients with higher expression of ERK in tumor tissue compared with nontumor tissue, the histologic finding was more progressed; but a similar tendency was not observed for cyclin D1. In patients with overexpression of HGF and c-Met, the expression level of ERK was significantly higher, but cyclin D1 expression was not. The detected level of cyclin D1 was significantly higher in patients with overexpressed ERK in tumor tissue. Values of ERK and c-Met were correlated, and IM presence was detected more frequently in patients with high expression of ERK and c-Met protein. Even after complete removal of visible IM tumor, recurrence tumors were detected within 6 months in 7 patients with high expressions of both ERK and c-Met protein.

Conclusions: Combination study of tumor expression of ERK might be useful to estimate the properties of hepatocellular carcinoma, especially for the presence of IM.

MeSH terms

  • Aged
  • Blotting, Western
  • Carcinoma, Hepatocellular / enzymology*
  • Cyclin D1 / biosynthesis
  • Extracellular Signal-Regulated MAP Kinases / biosynthesis*
  • Female
  • Gene Expression
  • Hepatocyte Growth Factor / biosynthesis
  • Humans
  • Liver Neoplasms / enzymology*
  • Male
  • Proto-Oncogene Proteins c-met / biosynthesis


  • Cyclin D1
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Extracellular Signal-Regulated MAP Kinases