Correlation of peritoneal dissemination and integrin alpha 3 expression in gastric cancer

Abstract

To clarify the interrelationship between alpha 3 integrin, subunit/E-cadherin expression and peritoneal dissemination in gastric cancer, alpha 3 integrin subunit and E-cadherin expression gas were immunohistochemically examined and were correlated with clinicopathologic parameters. Among 150 primary gastric cancers, alpha 3 integrin subunit and E-cadherin were strongly expressed in 96 (65%) and 88 (59%) tumors, respectively. Integrin alpha 3 expression was closely associated with peritoneal dissemiantion, but there was no relationship between integrin alpha 3 expression and histologic type, nodal status, macroscopic type or wall invasion. Furthermore, 22 (84%) of 26 tumors which recurred in peritoneum overexpressed integrin alpha 3 expression in primary tumors. All seven peritoneal foci obtained from peritoneal dissemination expressed integrin alpha 3 expression despite no integrin alpha 3 expression in two of these 7 primary tumors. Reduced E-cadherin expression in primary tumors was intimately associated with large tumor size (>6 cm), nodal involvement, peritoneal dissemination and positive serosal invasion. Peritoneal dissemination was most frequently found in the tumors with positive integrin alpha 3 expression and reduced E-cadherin expression. Patients with these type of tumor [E-cadherin expression (-), and integrin alpha 3 subunit (+)] showed the poorest prognosis as compared with the other groups of patients. These results indicate that upregulation of integrin alpha 3 expression and down regulation of E-cadherin might have an important role in the formation of peritoneal dissemination. These tumors have characteristics of easy detachment from the serosal surface via downregulation of E-cadherin and strong adhesion capacity to the peritoneum via up-regulation of integrin alpha 3 expression. The immunohisto-chemical combination analysis of E-cadherin and integrin alpha 3 expression on the primary gastric cancer may be a good screening method to predict peritoneal recurrence.