Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 as a prognostic factor in human colorectal carcinomas

BACKGROUND/AIMS: The urokinase pathway of plasminogen activation is known to be involved in proteolytic degradation of the extracellular matrix during carcinoma invasion. METHODOLOGY: We immunohistochemically examined 97 colorectal carcinomas for the expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1. (PAI-1) to investigate whether uPA and PAI-1 expressions could serve as prognostic parameters; the gene expression of uPA and PAI-1 in human colon cancer tissues was also analyzed using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The relative expression levels of uPA and PAI-1 mRNAs were well correlated with immunoreactivities of uPA and PAI-1, respectively (p<0.05). In immunohistochemical staining, diffuse specific staining was observed in the cytoplasm of carcinoma cells. uPA expression was detected in 57 carcinoma specimens (58.8%) and PAI-1 expression was detected in 36 specimens (37.1%). With regard to 5-year overall survival rate, patients whose tumors had positive uPA and negative PAI-1 immunoreactivities had a significantly poorer prognosis (p<0.05). In multivariate analysis, the combined variable of uPA and PAI-1 was shown to be an independent prognostic indicator. CONCLUSIONS: Our results suggest that immunohistochemical combined analysis of uPA and PAI-1 may be a useful prognostic factor in colorectal carcinoma patients.