The urokinase plasminogen activator system in angiosarcoma, Kaposi's sarcoma, granuloma pyogenicum, and angioma: An immunohistochemical study

Background: Extracellular matrix proteolysis is one of the most important steps in angiogenesis. The urokinase-type plasminogen activator system (uPAS), consisting of the urokinase plasminogen activator (uPA), the uPA receptor (uPA-R), and their corresponding inhibitors, PAI-1 and PAI-2, is thought to play a role in this process. Methods: We investigated the expression of the components of uPAS in angiosarcoma (AS, n=4), Kaposi's sarcoma (KS, n=31), granuloma pyogenicum (GP, n=25), angioma (AN, n=15), and healthy controls (CO, n=15) with immunohistochemical methods. Results: We found positive immunostaining for uPA-R and uPA in all cases of AS. Only two of four cases were positive for PAI-1, whereas all cases were negative for PAI-2. In KS, we observed positive immunostaining in 16 of 31 (51.6%) cases for uPA-R, in 11 of 31 (35.5%) cases for uPA, in 3 of 31 (9.6%) cases for PAI-1, and in 2 of 31 (6.4%) cases for PAI-2. The GP cases showed the following positive results: 4 of 25 (16%) for uPA-R, 6 of 25 (24%) for uPA, 10 of 25 (40%) for PAI-1, and 11 of 25 (44%) for PAI-2. Four cases (26.6%) of AN were positive for PAI-1 and five cases (25%) for PAI-2. In AN (n=15), there was staining for neither uPA nor uPA-R. In none of the controls (n=15) was immunostaining for the components of uPAS found in blood vessels. Conclusions: uPAS is involved in malignant, benign, and reactive proliferative angiomatous lesions, but is absent in normal blood vessels. The upregulation of uPA and its corresponding receptor, uPA-R, in AS and KS supports the hypothesis of the proliferative nature of these lesions; however, the upregulation of the inhibitors (PAI-1 and PAI-2) in benign and reactive proliferative angiomatous lesions (GP and AN) shows how this process may be limited.