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
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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.