Expression of Notch1, Jagged1 and beta-catenin and their clinicopathological significance in hepatocellular carcinoma

Neoplasma. 2009;56(6):533-41. doi: 10.4149/neo_2009_06_533.

Abstract

The Notch/Jagged signaling pathway is important for cellular differentiation and proliferation. Notch1/Jagged1 can either suppress or promote tumors depending on the cell type and context. beta-catenin, one of the mediators of the Wnt signalling pathway, represents a key element in one of the most important pathways of carcinogenesis. The aim of this study was to examine the expression of Notch1/Jagged1 and beta-catenin in hepatocellular carcinoma and to assign clinicopathological correlations. Immunohistochemical detection of Notch1/Jagged1 and beta-catenin was performed in tissue microarrays including 339 Hepatocellular carcinomas, 174 adjacent non-tumor livers and 94 normal livers. The results showed that the rate of expression was 66%, 98% and 97% for Notch1 and 36%, 85% and 92% for Jagged1 respectively in hepatocellular carcinoma, adjacent non-tumor liver and normal liver. Decreased expression of Notch1/Jagged1 was correlated significantly with Edmondson-Steiner grade. However, nuclear beta-catenin was expressed in 37% of hepatocellular carcinoma tissue, which was significantly higher than its non-tumor counterparts. Increased nuclear beta-catenin expression was correlated with HBs-Ag status and Edmondson-Steiner grade. Moreover, The positive expression of Notch1 was parallel with Jagged1 expression (r =0.235, p=0.000) and reduced Notch1 expression was associated with increased beta-catenin expression in hepatocellular carcinoma (r =-0.125, p =0.023). In conclusion, Notch1/Jagged1 were frequently low expressed in hepatocellular carcinoma and correlated with the high expression of beta-catenin suggesting that downregulation of Notch1/Jagged1 signaling may sustain tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Calcium-Binding Proteins / metabolism*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / secondary
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Infant
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Jagged-1 Protein
  • Liver / metabolism
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Prognosis
  • Receptor, Notch1 / metabolism*
  • Serrate-Jagged Proteins
  • Young Adult
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • NOTCH1 protein, human
  • Receptor, Notch1
  • Serrate-Jagged Proteins
  • beta Catenin