Prognostic significance of p21WAF1/CIP1, p27Kip1, p53 and E-cadherin expression in gastric cancer
- Armando Gamboa-Dominguez (agamboad{at}quetzal.innsz.mx)
- Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico
- Stefan Seidl (stefan.seidl{at}lrz.tu-muenchen.de)
- Edgardo Reyes-Gutierrez (guisbato{at}prodigy.net.mx)
- Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico
- Christine Hermannstädter (chrischie75{at}web.de)
- Leticia Quintanilla-Martinez (quintanilla-fend{at}gsf.de)
- Raymonde Busch (raymonde.busch{at}imse.med.tu-muenchen.de)
- Heinz Höfler (hoefler{at}lrz.tu-muenchen.de)
- Falko Fend (fend{at}lrz.tu-muenchen.de)
Abstract
Background: Gastric carcinoma is characterized 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 tumor 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 so far.
Aims: The aim of the study was a combined evaluation of 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 and expression levels were correlated with histotype, tumor 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.
