CORRELATION OF PERITONEAL DISSEMINATION AND INTEGRIN ALPHA-3 EXPRESSION IN GASTRIC-CANCER

To clarify the interrelationship between alpha 3 integrin, subunit/E-c adherin expression and peritoneal dissemination in gastric cancer, alp ha 3 integrin subunit and E-cadherin expression gas were immunohistoch emically examined and were correlated with clinicopathologic parameter s. Among 150 primary gastric cancers, alpha 3 integrin subunit and E-c adherin were strongly expressed in 96 (65%) and 88 (59%) tumors, respe ctively. Integrin alpha 3 expression was closely associated with perit oneal dissemiantion, but there was no relationship between integrin al pha 3 expression and histologic type, nodal status, macroscopic type o r 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 exp ressed integrin alpha 3 expression despite no integrin alpha 3 express ion 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 in vasion. Peritoneal dissemination was most frequently found in the tumo rs with positive integrin alpha 3 expression and reduced E-cadherin ex pression. Patients with these type of tumor [E-cadherin expression (-) , and integrin alpha 3 subunit (+)] showed the poorest prognosis as co mpared with the other groups of patients. These results indicate that upregulation of integrin alpha 3 expression and down regulation of E-c adherin might have an important role in the formation of peritoneal di ssemination. These tumors have characteristics of easy detachment from the serosal surface via downregulation of E-cadherin and strong adhes ion capacity to the peritoneum via up-regulation of integrin alpha 3 e xpression. 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.