H. Ito et al., PROGNOSTIC RELEVANCE OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR (UPA) AND PLASMINOGEN-ACTIVATOR INHIBITORS PAI-1 AND PAI-2 IN GASTRIC-CANCER, Virchows Archiv, 427(5), 1996, pp. 487-496
Expression of urokinase-type plasminogen activator (uPA), plasminogen
activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (P
AI-2) was evaluated in 125 surgically resected gastric cancers by immu
nohistochemical analysis. Tissue was stained immunohistochemically wit
h a monoclonal antibody against human uPA and monoclonal antibodies ag
ainst human PAI-1 and PAI-2. In addition, DNA ploidy patterns were det
ermined by cytofluorometer after staining with propidium iodide. We fo
und that 82 (66%) of the 125 gastric cancers expressed uPA as diffuse
cytoplasmic staining, as intensely outlined luminal borders. PAI-1 exp
ression was observed in 62 (50%) of 125 gastric cancer as a fine, diff
use and granular pattern in the cytoplasm. PAI-2 expression was observ
ed in 65 (52%) of the 125 gastric cancers as a diffuse cytoplasmic sta
ining. uPA-positive rumours showed a higher incidence of infiltration,
lymph node metastasis and peritoneal dissemination than uPA-negative
ones. Patients with uPA-positive tumours proved to have a significantl
y poorer prognosis than those with negative ones. PAI-1-negative tumou
rs showed a higher incidence of liver metastasis and carried a poorer
prognosis than PAI-1-positive ones. There was no significant correlati
on between uPA or PAI-1 expression and DNA ploidy patterns. Conversely
, there was no significant relationship between PAI-2 expression and c
linicopathological parameters and prognosis. According to the expressi
on of uPA and PAI-1 status, groups of 19 uPA(-)/PAI-1(-), 44 uPA(+)/PA
I-1(-), 23 uPA(-)/PAI-1(+) and 39 uPA(+)/PAI-1(+) were subdivided. Tum
ours with uPA(+)/PAI-1(-) had a significantly higher incidence of live
r metastasis, lymph node metastasis and serosal invasion than the othe
r groups of tumours. Patients with uPA(+)/PAI-1(-) tumours had a signi
ficantly poorer prognosis than those with uPA(-)/PAI-1(+) tumours. The
se results indicate that uPA expression is a useful biological prognos
tic indicator, and that uPA and PAI-1 may play an important part in th
e tumour progression and metastasis in gastric cancer.