Prognostic significance of p21WAF1/CIP1, p27Kip1, p53 and E-cadherin expression in gastric cancer

J Clin Pathol. 2007 Jul;60(7):756-61. doi: 10.1136/jcp.2006.038976. Epub 2007 May 4.

Abstract

Background: Gastric carcinoma is characterised by numerous genetic and epigenetic alterations that influence cell cycle progression, apoptosis and DNA repair. These alterations include down-regulation of the cyclin-dependent kinase (CDK) inhibitors p21(WAF1/CIP1) and p27(Kip1), and mutations of the tumour suppressor protein p53 and the cell adhesion molecule E-cadherin. Combined evaluation of the prognostic significance of these alterations has not been reported in Mexican Mestizo patients.

Aims: To evaluate p21(WAF1/CIP1), p27(Kip1), p53 and E-cadherin protein expression, including mutant E-cadherin variants with deletion of exon 8 (del 8) or 9 (del 9), in gastric cancer from Mexican patients.

Methods: Immunohistochemistry for the above-mentioned markers, including mutation-specific E-cadherin antibodies, was carried out in 69 gastric carcinomas; expression levels were correlated with histotype, tumour stage and prognosis.

Results: Expression of p21(WAF1/CIP1) alone or in combination with p27(Kip1) or in the absence of p53 was associated with favourable prognosis. Staining of del 8 and del 9 E-cadherin was found exclusively in patients negative for p53 and positive for p21(WAF1/CIP1), suggesting that the p21(WAF1/CIP1) regulatory function of p53 was intact.

Conclusion: Combined evaluation of the prognostic significance of cell cycle regulators and E-cadherin should be performed. Even though patients negative for p53 and positive for p21(WAF1/CIP1) have a favourable prognosis, it may have a negative influence on prognosis if they acquire in addition E-cadherin mutations which have been shown previously to be associated with poor survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cadherins / metabolism
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Prognosis
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Neoplasm Proteins
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase Inhibitor p27