Caspase-3 expression in human gastric carcinoma and its clinical significance

Oncology. 2004;66(3):201-9. doi: 10.1159/000077996.


Objectives: Caspase-3 is one of the most important molecules in the apoptosis cascade, and the relationship between caspase-3 expression and prognosis has been reported in many types of malignancies. However, the involvement of caspase-3 in human gastric carcinoma is not fully understood. We evaluated caspase-3 expression in human gastric carcinoma to clarify the clinicopathological importance and investigated the apoptosis avoidance mechanism by an immunohistological method.

Methods: Specimens from 151 patients who underwent gastrectomy at the Department of Surgery and Surgical Basic Science of Kyoto University Hospital were investigated. Caspase-3 expression in cancer cells was evaluated by comparing its expression in the germinal center of the lymphoid follicle, and was quantified as the caspase-3 expression index (C3EI). C3EI was compared with the expression of Bcl-2 and the TdT-mediated dUTP biotin nick-end labeling (TUNEL) in 80 randomly selected cases. Actual activation of caspase-3 was determined by immunohistochemistry using monoclonal antibody that recognizes only activated caspase-3.

Results: C3EI correlated significantly with lymph node metastasis (negative 105.5-78.7, positive 153.8 +/- 66.1 p = 0.001) and the lower C3EI group had a better prognosis than the higher group (log-rank test, p = 0.0001). Cox multivariate analysis showed that age, operation curability, tumor invasion and C3EI were significant independent determinants of overall survival. Bcl-2 and TUNEL staining had no significant correlations with C3EI. Immunohistochemistry of activated caspase-3 revealed that most caspase-3 in gastric cancer cells was not activated, in accordance with TUNEL assay.

Conclusions: Our results show that C3EI is a novel, independent prognostic factor in gastric cancer patients and cancer cells may avoid apoptosis by inhibiting caspase-3 activation.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Apoptosis
  • Biomarkers, Tumor / analysis*
  • Caspase 3
  • Caspases / analysis*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Middle Aged
  • Photomicrography
  • Predictive Value of Tests
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Stomach Neoplasms / chemistry
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery
  • Survival Analysis


  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • CASP3 protein, human
  • Caspase 3
  • Caspases