ORIGINAL ARTICLE

Prognostic significance of p21^WAF1/CIP1, p27^Kip1, p53 and E-cadherin expression in gastric cancer

Armando Gamboa-Dominguez¹, Stefan Seidl², Edgardo Reyes-Gutierrez¹, Christine Hermannstädter², Leticia Quintanilla-Martinez³, Raymonde Busch⁴, Heinz Höfler², Falko Fend² and Birgit Luber²

¹ Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
² Technische Universität München, Klinikum rechts der Isar, Institut für Allgemeine Pathologie und Pathologische Anatomie, München, Germany
³ GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Pathologie, Neuherberg, Germany
⁴ Technische Universität München, Klinikum rechts der Isar, Institut für Medizinische Statistik und Epidemiologie, München, Germany

Correspondence to:
Correspondence to:
Dr Birgit Luber
Institut für Allgemeine Pathologie und Pathologische Anatomie, Trogerstr. 18, 81675 München, Germany; luber{at}lrz.tu-muenchen.de

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.

Abbreviations: 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

Keywords: p21WAF1/CIP1; p27Kip1; p53; E-cadherin; gastric cancer

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