E-CADHERIN AND UROKINASE-TYPE PLASMINOGEN-ACTIVATOR TISSUE STATUS IN GASTRIC-CARCINOMA

Background. E-cadherin (ECD) is known to be an invasion suppressor gen e, and urokinase-type plasminogen activator (uPA) plays a central role in infiltration of solid cancers. Methods. To elucidate the relations hip between expression of these factors and metastasis in patients wit h gastric cancer, the authors examined immunohistochemically a combina tion analysis of uPA and E-cadherin expression in 98 primary tumors, a nd the results were correlated with several parameters related to meta stasis. Results. Among 125 tumors, 42 (34%) were evaluated as having E -cadherin expression (E-cadherin-positive), and the other 83 (66%) wer e defined as having reduced E-cadherin expression (E-cadherin-negative ). uPA immunoreactivity was observed in 82 tumors (66%). There were fo ur subtypes of patterns of uPA and E-cadherin expression: 22 uPA-negat ive/E-cadherin-positive, 17 uPA-negative/E-cadherin-negative, 21 uPA-p ositive/E-cadherin-positive, and 65 uPA-positive/E-cadherin-negative. uPA overexpression and reduced E-cadherin expression were associated w ith lymph node metastasis, vessel invasion, serosal involvement, and p oor prognosis. In addition, uPA-positive/E-cadherin-negative tumors we re associated significantly with large tumors, positive serosal invasi on, lymph node involvement, and poor prognosis. Patients with uPA-posi tive/E-cadherin-negative expression had the poorest prognoses, compare d with the three other groups of patients. uPA-positive/E-cadherin-neg ative tumors had a fourfold relative risk of death when compared with uPA-negative/E-cadherin-positive tumors. A Cox proportional hazard mod el projected lymph node status as the strongest of the prognostic vari ables, followed by DNA ploidy patterns and uPA/E-cadherin tissue statu s. Conclusions. These results indicate that immunohistochemical combin ation analysis of uPA and E-cadherin expression may be a powerful aid in evaluating metastatic potential or the prognosis of patients with g astric cancer.