Immunohistochemical expression of uPA, uPAR, and PAI-1 in breast carcinoma- Fibroblastic expression has strong associations with tumor pathology

The urokinase-type plasminogen activator (uPA) system has been implicated i n tumor spread. We have used immunohistochemistry to examine three componen ts of this system, ie, uPA, uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-I), in a pilot study on 142 cases of breast carcinoma. We wished to determine whether there were any relationships between expression of the proteins in either tumor cells or fibroblasts and clinical and path ological features. Strong uPA expression in each cell type was significantl y related to high tumor grade (P = 0.013 and 0.008, respectively), and was more common in invasive than in in situ carcinomas (P < 0.0001), Fibroblast ic expression of uPAR was only related to the presence of invasion (P < 0.0 001), Strong PAI-1 expression in both cell types was seen in high-grade tum ors (tumor cells, P = 0.012; fibroblasts, P < 0.001), but only fibroblastic expression was related to the presence of invasion (P = 0.042). Fibroblast ic expression of both uPA and uPAR were positively correlated with tumor si ze. Although patients with strong fibroblastic expression of uPA showed a t endency toward a shorter time to relapse, none of the plasminogen activator proteins were significantly associated with relapse-free survival, These r esults suggest that strong expression of uPA, uPAR, and PAI-1 in fibroblast s rather than in tumor cells have the most impact on the clinical behavior of breast cancer. Larger prospective studies are needed to confirm these fi ndings.