Beta-catenin expression in hepatocellular carcinoma: a possible participation of beta-catenin in the dedifferentiation process

J Gastroenterol Hepatol. 2002 Sep;17(9):994-1000. doi: 10.1046/j.1440-1746.2002.02774.x.

Abstract

Background: beta-Catenin is known as a multifunctional protein acting as a regulator of the cadherin-mediated cell-cell adhesion system and in the Wingless/Wnt signal transduction pathway. Recent studies reported mutation of the beta-catenin gene in some tissues of hepatocellular carcinoma (HCC).

Methods: 'Nodule-in-nodule' appearance is a feature of well-differentiated HCC containing a distinct nodule of less-differentiated cancer tissue inside, and it is presumed to be a morphological expression of the dedifferentiation process. The present study immunohistochemically investigated the beta-catenin expression according to the dedifferentiation process of HCC, that is, in small well-differentiated HCC with indistinct margins, HCC with a 'nodule-in-nodule' appearance, moderately differentiated HCC, which does not have a 'nodule-in-nodule' appearance, and sarcomatous HCC.

Results: The expression of beta-catenin was observed in approximately 70% of small well-differentiated HCC with indistinct margins. In HCC with a 'nodule-in-nodule' appearance, membranous expression of beta-catenin was higher in the well-differentiated cancer tissues than in the less-differentiated cancer tissues (P < 0.01), cytoplasmic expression was higher in the less-differentiated cancer tissues (P < 0.01), and nuclear expression was higher in the less-differentiated cancer tissues (P < 0.001). In moderately differentiated HCC, tumors with membranous expression of beta-catenin had more frequent intrahepatic metastasis than those without having the expression (P < 0.001).

Conclusions: Accumulation of beta-catenin was already present in the early stage of HCC, and in less-differentiated cancer tissue the membranous expression of beta-catenin could be related to intrahepatic metastasis.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Cadherins / biosynthesis
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Differentiation
  • Cell Division
  • Cytoskeletal Proteins / biosynthesis*
  • Disease Progression
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Trans-Activators / biosynthesis*
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Ki-67 Antigen
  • Trans-Activators
  • beta Catenin