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 p21WAF1/CIP1 and p27Kip1, 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 p21WAF1/CIP1, p27Kip1, 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 p21WAF1/CIP1 alone or in combination with p27Kip1 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 p21WAF1/CIP1, suggesting that the p21WAF1/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 p21WAF1/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.
- CDK, cyclin dependent kinase
- del 8 E-cadherin, E-cadherin with deletion of exon 8
- del 9 E-cadherin, E-cadherin with deletion of exon 9
- TNM, tumour node metastasis
- gastric cancer
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
Published Online First 4 May 2007
Funding: The study was supported by a grant to Drs B Luber and I Becker from the Wilhelm-Sander-Stiftung (Nr 1999.118.2).
Competing interests: None.