IN-SITU STROMAL EXPRESSION OF THE UROKINASE PLASMIN SYSTEM CORRELATESWITH EPITHELIAL DYSPLASIA IN COLORECTAL ADENOMAS/

An increase of urokinase-type plasminogen activator (uPA) and a decrea se of tissue-type PA (tPA) have been associated with the transition fr om normal to adenomatous colorectal mucosa. Serial sections from 25 ad enomas were used to identify PA-related caseinolytic activities by in situ zymography, blocking selectively uPA or tPA. The distribution of uPA, tPA, and type 1 PA inhibitor mRNAs was investigated by nonradioac tive in situ hybridization, and the receptor for uPA was detected by i mmunostaining. Low- and high-grade epithelial cell dysplasia was mappe d histologically. Results show that 23 of 25 adenomas expressed uPA-re lated lytic activity located predominantly in the periphery whereas tP A-related activity teas mainly in central areas of adenomas In 15 of 2 5 adenomas, uPA mRNA was expressed in stromal cells clustered in foci that coincided with areas of uPA lytic activity. The probability of fi nding uPA mRNA-reactive cells was significantly higher in areas with h igh-grade epithelial dysplasia, uPA receptor teas mainly stromal and e xpressed at the periphery. Type I PA inhibitor mRNA cellular expressio n was diffuse in the stroma, in endothelial cells, and in a subpopulat ion of alpha-smooth muscle cell actin-reactive cells, These results sh ow that a stromal up-regulation of the uPA/plasmin system is associate d with foci of severe dysplasia in a subset of colorectal adenomas.