Frequent translocalization of beta-catenin in gastric cancers and its relevance to tumor progression.

Altered distribution of beta-catenin has been found in many human malignancies including gastric cancer, but its reason(s) and biological implications have not yet been fully clarified. By the methods of frozen tissue array-based immunohistochemistry, RT-PCR and PCR-SSCP followed by DNA sequencing, the patterns of beta-catenin distribution in the subtypes of gastric cancers and their premalignant and non-cancerous counterparts were examined and the potential correlation of beta-catenin alteration with invasion was elucidated. Membranous beta-catenin was detected constantly in non-cancerous mucosa but became reduced or absent in cancer tissues. The cytoplasmic and nuclear accumulation of beta-catenin could be observed in premalignant (atrophic gastritis and intestinal metaplasia) and cancer tissues, particularly in those infiltrated into deep muscular region. beta-catenin mutation was not detected in all of tissue samples with and without translocalized beta-catenin. These results indicate that beta-catenin translocalization is a common phenomenon in gastric cancers as well as their related lesions. The loss of membranous and the gain of cytoplasmic and nuclear beta-catenin in gastric cancers checked in this study are not due to the mutational event. beta-catenin molecules translocalized in the nuclei are closely correlated with tumor invasion.