MUTATIONS OF P53, E-CADHERIN, ALPHA-CATENIN AND BETA-CATENIN GENES AND TYROSINE PHOSPHORYLATION OF BETA-CATENIN IN HUMAN GASTRIC CARCINOMAS

We investigated whether dysfunction of p53 and E-cadherin participate in invasiveness and metastasis of human gastric carcinoma. We examined twenty-five human gastric carcinomas for p53, E-cadherin, alpha- and beta-catenin gene alteration by the reverse transcription-polymerase c hain reaction-single strand conformation polymorphism (RT-PCR-SSCP) me thod and sequencing analysis. Three samples (13%) showed p53 gene muta tion (two missense mutations and 6 bp deletion). 25% (3/12) of the car cinomas with lymph node metastasis had p53 gene mutations. One sample (4%) showed E-cadherin silent mutation. We were not able to detect alp ha- or beta-catenin gene alteration. Therefore we investigated tyrosin e-phosphorylation of E-cadherin, a and beta-catenin. Tyrosine-phosphor ylated beta-catenin was detected in 13% (2/15) of poorly differentiate d carcinomas. These results suggest that the p53 gene mutations have s ome correlation with lymph node metastasis, and tyrosine phosphorylati on of beta-catenin rather than cadherin/catenin gene mutation is at le ast partly responsible for the loosening of cell-cell contact and inva siveness of poorly differentiated carcinomas.