PROGNOSTIC RELEVANCE OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR (UPA) AND PLASMINOGEN-ACTIVATOR INHIBITORS PAI-1 AND PAI-2 IN GASTRIC-CANCER

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.