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.