Tumour suppressor gene expression correlates with gastric cancer prognosis

J Pathol. 2003 May;200(1):39-46. doi: 10.1002/path.1288.


The loss of tumour suppressor genes (TSGs) is a key event in many human cancers, including gastric carcinoma. Many TSG candidates have been studied, but their roles in gastric carcinogenesis remain unclear. To clarify the clinical significance of TSG expression in gastric carcinoma, the expression of various TSG candidates (p53, E-cadherin, FHIT, smad4, rb, VHL, PTEN, MGMT, p16, and KAI1), as well as other proteins (bcl-2, MUC1, MUC2, MUC5AC, MUC6, CEA, CD44, beta-catenin, C-erbB2, and cyclin B2), was evaluated immunohistochemically in 329 consecutive gastric carcinomas using the tissue array method. The overexpression of p53 and MUC1 (p < 0.01) and the loss of expression of smad4 (p = 0.04), FHIT (p = 0.03), MGMT (p = 0.01), E-cadherin, KAI1, and PTEN (p < 0.01) were found to be significantly associated with poor gastric carcinoma prognosis. Seven out of eight survival-associated proteins were found to be protein products of TSGs. The gastric carcinomas were divided into five groups according to the grade of alteration in TSG expression. No TSG expression loss was found in 32 cases (TSG1). One TSG loss was found in 47 cases (TSG2), two in 67 cases (TSG3), three or four in 64 cases (TSG4), and five, six, or seven in 38 cases (TSG5). The grade of TSG expression was confirmed to be significantly associated with WHO classification (p = 0.04), pTNM stage, lymphatic invasion, and patient survival (p < 0.01 for the latter three). By multivariate analysis, the grade of TSG expression was found to be significantly and independently associated with patient survival (p < 0.01). In conclusion, the findings of this study suggest that the cumulative loss of TSG expression in gastric carcinoma is important in determining patient survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases*
  • Antibodies, Neoplasm / genetics
  • Antigens, CD*
  • Cadherins / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Gene Expression*
  • Genes, Tumor Suppressor / physiology*
  • Histocytological Preparation Techniques / methods
  • Humans
  • Immunohistochemistry / methods
  • Kangai-1 Protein
  • Male
  • Membrane Glycoproteins / genetics
  • Middle Aged
  • Mucin-1 / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Proteins / genetics
  • O(6)-Methylguanine-DNA Methyltransferase / genetics
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / genetics
  • Prognosis
  • Proto-Oncogene Proteins*
  • Smad4 Protein
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Trans-Activators / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins / genetics


  • Antibodies, Neoplasm
  • Antigens, CD
  • CD82 protein, human
  • Cadherins
  • DNA-Binding Proteins
  • Kangai-1 Protein
  • Membrane Glycoproteins
  • Mucin-1
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • fragile histidine triad protein
  • O(6)-Methylguanine-DNA Methyltransferase
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Acid Anhydride Hydrolases