Relationship between E-cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl-2 expression and Ki-67 staining in diffuse-type gastric carcinoma

Int J Cancer. 2003 Mar 10;104(1):60-5. doi: 10.1002/ijc.10879.


E-cadherin mutations are found in 50% of diffuse-type gastric carcinoma, but not in intestinal gastric carcinoma. Because cell-cell adhesion mediated by E-cadherin plays an important role in epithelial cell survival, E-cadherin mutations could alter the apoptotic behavior of tumor cells. p53 and Bcl-2 family members are also important regulators of cellular apoptosis. This is the first study that investigates the relationship between E-cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl-2 expression, and Ki-67 expression in diffuse-type gastric carcinoma (24 cases, E-cadherin mutation status: wild-type in 8 patients and mutant in 16 patients). The mutation status of exons 5-8 of p53 was analyzed by denaturing high pressure liquid chromatography (DHPLC) in formalin-fixed, paraffin-embedded tumor sections, followed by direct sequencing of cases with aberrant chromatographic patterns. p53 mutations were found in 1 of 8 tumors without E-cadherin mutation (12.5%) and in 1 of 16 tumors with E-cadherin mutation (6.3%), a difference that was not statistically significant (p = 1.00). p53 accumulation was found in 8 of 24 tumors (33.3%) by immunohistochemical staining. p53 accumulation was significantly more frequent in tumors without E-cadherin mutations (5 of 8 tumors, 62.5%) than in gastric carcinoma tissues with E-cadherin mutations (3 of 16 tumors, 18.8%, p = 0.03). Bcl-2 staining was not observed in gastric carcinoma cells without E-cadherin mutations, but was detectable in 5 of 16 tumors with E-cadherin mutations (31.3%), a difference that was not statistically significant (p = 0.13). No relationship was observed between Ki-67 staining and the E-cadherin mutation status (p = 1.00). These data suggest that the presence of E-cadherin mutations can significantly alter the accumulation of the apoptosis-regulating p53 protein, whereas no correlation with the p53 mutation status or with Ki-67 staining was observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Apoptosis / genetics
  • Cadherins / genetics
  • Cadherins / physiology*
  • Cell Adhesion
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Exons / genetics
  • Genes, bcl-2*
  • Genes, p53*
  • Humans
  • Ki-67 Antigen / analysis*
  • Mutation*
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Tumor Suppressor Protein p53 / biosynthesis*


  • Cadherins
  • DNA, Neoplasm
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53