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.