Positive association of up-regulated Cripto-1 and down-regulated E-cadherin with tumour progression and poor prognosis in gastric cancer

Histopathology. 2008 Apr;52(5):560-8. doi: 10.1111/j.1365-2559.2008.02971.x. Epub 2008 Feb 28.

Abstract

Aims: Cripto-1 may be capable of up-regulating signalling molecules associated with epithelial-to-mesenchymal transition (EMT), an important event characterized by loss of E-cadherin during malignant tumour progression and metastasis. The aim was to investigate the expression of Cripto-1 and E-cadherin in relation to clinicopathological features and patient prognosis of gastric cancer.

Methods and results: The expression of Cripto-1 and E-cadherin was studied by immunohistochemistry in 118 gastric cancer cases. Up-regulated Cripto-1 (CR+) was found in 54% (64/118) of cases, whereas down-regulated E-cadherin (E-cad-) was found in 70% (83/118) of cases. Either CR+ or E-cad- was associated with lymph node metastasis, liver metastasis and late TNM stage (P < 0.05). Patients with either CR- or E-cad+ showed higher 5-year survival rates than those with CR+ or E-cad- (P = 0.0012 and P = 0.0017, respectively). When combined, evaluation of these two proteins, simultaneous CR+ and E-cad- (CR+/E-cad-) in cancer was strongly associated with the above three aggressive clinicopathological features (P < 0.001) and indicated the worst patient survival (P = 0.0001). Multivariate analysis revealed that CR+/E-cad- was an independent prognostic factor in gastric cancer.

Conclusions: Combined analysis of Cripto-1 and E-cadherin has significant value in evaluating the metastatic potential of gastric cancer and predicting patient prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Cadherins / metabolism*
  • Disease Progression
  • Down-Regulation
  • Epidermal Growth Factor / metabolism*
  • Female
  • GPI-Linked Proteins
  • Gastrectomy
  • Humans
  • Immunoenzyme Techniques
  • Intercellular Signaling Peptides and Proteins
  • Lymph Nodes / pathology
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Prognosis
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Survival Rate
  • Up-Regulation

Substances

  • Cadherins
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • TDGF1 protein, human
  • Epidermal Growth Factor