Relationship Between Abnormal Expression Of E-cadherin-catenin Complex And Biological Behaviors Of Gastric Carcinoma

It is well-known that anchorage of cells to substrate is critical for the integrity of many cell types including epithelial cells. The cadherins are a major class of adhesion molecules which play an important role in the homotypic cell-cell adhesion and hence cancer cell metastasis and invasion.E-cadherin is a member of the cadherin family which is expressed in all epithelial cells. It is a calcium-dependent cell adhesion molecule that binds to other E-cadherin molecules on adjacent cells and is located at the adhesion junction of epithelial cells. Functional cadherin-dependent cell adhesion requires the formation of complexes between E-cadherin and the cytoplasmic proteins known as the catenins. The catenin, which interacts with the cytoplasmic domain of E-cadherin, consists of at least two proteins: α- and β-catenin.β- catenin forms a complex with E-cadherin, while α- catenin links this complex to the actin cytoskeleton. It is postulated that changes in cell-cell and cell-matrix interactions account for the ability of cancer cells to cross normal tissue boundaries and metastasize. In addition, loss of cell adhesion may contribute to loss of contact inhibition and thus play a role at the earlier stage of the neoplastic process.Studies have shown that the E-cadherin-mediated cell adhesion system in human cancers is inactivated by multiple mechanisms, including: ①inactivation of the E-cadherin-mediated cell adhesion system as a result of genetic alteration; ② inactivation of the E-cadherin-mediated cell adhesion system due to reduced expression; ③ CpG methylation around the promoter region was considered a possible mechanism of E-cadherin gene inactivation in human cancers; ④ inactivation of the E-cadherin-mediated cell adhesion system by tyrosine phosphorylation of β-catenin.In this study, we investigated the expression pattern of E-cadherin or β- catenin in gastric cancers, dysplasia, intestinal metaplasia, atrophic gastritis. The possible relationship between the expression of the E-cadherin - catenin complex and the tumor clinicopathology, as well as its potential value in the evaluation of patient survival were also discussed.Our main finding and conclusions were as follows:1. Immunohistochemical staining of E-cadherin, α-catenin, and β-catenin was performed using paraffin specimens of 148 gastric carcinomas, and gastric biopsy from 44gastric mucosal dysplasia, and 25 intestinal metaplasia, 28 atrophic gastritis and 12 healthy controls. The abnormal expression rate of E-cadherin, α-catenin and β-catenin in the tissues of gastric carcinomas were 44.6%, 73.6%, and 43.2%, respectively. The total abnormal expression rate of E-cadherin-catenin complex in 148 cases of gastric carcinoma was 91.9%. Reduced expression of E-cadherin, α-catenin and β-catenin significantly correlated with tumor differentiation status (P <0.005). The rate of abnormal β-catenin staining was higher in tumors with positive lymph node metastasis and with distant metastasis than that in tumors without lymph node metastasis and distant metastasis (P <0.025,P <0.005,respectively). Furthermore, 36%, 16% and 43% of gastric dysplasia were stained abnormally for E-cadherin, β- and α-catenin respectively. In conclusion, our results indicate that abnormal expression of the E-cadherin- catenin complex occurs frequently in gatric carcinoma, closely related to its histogenesis. Abnormal expression of the E-cadherin- catenin complex in gastric dysplasia may be an early event in the tumorigenesis. 2. Survival data were obtained for 113 of the patients. Kaplan-Meier curves were computed to compare survival of patients with normal versus abnormal expression of E-cadherin, α-and β-catenin. The overall median survival of patients in this study was 1103 days (range 78-2365). A survival advantage was not noted in the tumors retained normal staining of E-cadherin and α-catenin. The average survival time for patients with abnormal expression of β-catenin was 764±110 days, as opposed to the survival time of 1798 ±10...