E-cadherin and urokinase-type plasminogen activator tissue status in gastric carcinoma

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Abstract
Background. E‐cadherin (ECD) is known to be an invasion suppressor gene, and urokinase‐type plasminogen activator (uPA) plays a central role in infiltration of solid cancers. Methods. To elucidate the relationship between expression of these factors and metastasis in patients with gastric cancer, the authors examined immunohistochemically a combination analysis of uPA and E‐cadherin expression in 98 primary tumors, and the results were correlated with several parameters related to metastasis. Results. Among 125 tumors, 42 (34%) were evaluated as having E‐cadherin expression (E‐cadherin‐positive), and the other 83 (66%) were defined as having reduced E‐cadherin expression (E‐cadherin‐negative). uPA immunoreactivity was observed in 82 tumors (66%). There were four subtypes of patterns of uPA and E‐cadherin expression: 22 uPA‐negative/E‐cadherin‐positive, 17 uPA‐negative/E‐cadherin‐negative, 21 uPA‐positive/E‐cadherin‐positive, and 65 uPA‐positive/E‐cadherin‐negative. uPA overexpression and reduced E‐cadherin expression were associated with lymph node metastasis, vessel invasion, serosal involvement, and poor prognosis. In addition, uPA‐positive/E‐cadherin‐negative tumors were associated significantly with large tumors, positive serosal invasion, lymph node involvement, and poor prognosis. Patients with uPA‐positive/E‐cadherin‐negative expression had the poorest prognoses, compared with the three other groups of patients. uPA‐positive/E‐cadherin‐negative tumors had a fourfold relative risk of death when compared with uPA‐negative/E‐cadherin‐positive tumors. A Cox proportional hazard model projected lymph node status as the strongest of the prognostic variables, followed by DNA ploidy patterns and uPA/E‐cadherin tissue status. Conclusions. These results indicate that immunohistochemical combination analysis of uPA and E‐cadherin expression may be a powerful aid in evaluating meta‐static potential or the prognosis of patients with gastric cancer. Cancer 1995;76:941–53.