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The urokinase-type plasminogen activator (UPA) and its inhibitor PAI-1 are thought to play an important part in gastric cancer (GC) invasion and metastasis. Little is known about the behavior and prognostic impact of the receptor for UPA (UPAR). The aims of the present study were: (1) to measure UPAR, UPA and PAI-1 levels in GC and in non-malignant tissue distant from the tumor (NORM); (2) to evaluate their relationship with histomorphological parameters; and (3) to determine their prognostic value. UPAR, UPA and PAI-1 levels were determined by ELISA in GC and NORM samples from 20 patients with GC undergoing surgery. The GC was also examined in terms of the presence (n = 10) or absence (n = 10) of metastasis, differentiation (five differentiated, 15 undifferentiated) and histotype. Survival was analysed using life table analysis. UPAR, UPA and PAI-1 were significantly higher in GC vs NORM, in the presence of metastasis (UPAR, UPA) and in undifferentiated GC (UPAR, PAI-1). UPAR significantly correlated with UPA and PAI-1. Low levels of UPAR (P = 0.04), UPA (P = 0.007) and PAI-1 (P = 0.02) were associated with a better survival. Our results demonstrate a sharp increase in UPAR in GC and suggest a prognostic role for it. The concomitant activation of UPAR, UPA and PAI-1 in GC confirm the important role of the plasminogen activator system in the process of invasion and metastasis.

Background: Cysteine proteases [cathepsin B (CATB), cathepsin L (CATL)], the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) play an important part in cancer invasion. No data are available on the relationship between these proteases and gastric precancerous changes., Aims: To determine CATB, CATL, UPA, PAI-1 in chronic atrophic gastritis, intestinal metaplasia and gastric epithelial dysplasia, as precancerous changes, and to compare these data with those obtained in gastric cancer., Patients: Endoscopic biopsies were obtained from 12 patients with gastric cancer (cancerous tissue), 33 patients with chronic atrophic gastritis (all with intestinal metaplasia and 12 with dysplasia) and from 47 control subjects, for a total of 92 patients., Methods: Antigen concentrations were measured using ELISA methods. Immunohistochemistry was performed using monoclonal anti-CATB and anti-PAI-1 antibodies., Results: CATB, CATL, UPA and PAI-1 were significantly higher in chronic atrophic gastritis than in controls (CATB: P < 0.001; CATL: P < 0.005; UPA: P < 0.000001; PAI-1: P < 0.005). The same was observed for cancer. CATB and UPA were significantly higher in chronic atrophic gastritis, with versus without dysplasia (P < 0.05). Dysplastic epithelia showed strong immunoreactivity to PAI-1 and CATB., Conclusions: Our study demonstrates that cathepsins, UPA and PAI-1 may have a role not only in the process of cancer invasion, but also in the progression of precancerous changes into cancer.

Cysteine proteases (cathepsin B and L), the serine protease urokinase-type plasminogen activator and its inhibitor type-1 play an important part in cancer invasion and metastasis. The authors determined the protease concentrations in gastric cancer tissues, using the ELISA method, in patients with gastric cancer. They evaluated the prognostic role of proteases and the relationship that these proteases may have with other histomorphological prognostic parameters such as tumor staging, grading, histotype, Borrmann classification. The Cox survival analysis showed that cathepsin B (p = 0.002), urokinase-type plasminogen activator (p = 0.0001) and the inhibitor type-1 (p = 0.0004) significantly correlated with poor prognosis. The tumor staging, grading, Borrmann classification correlated also significantly with survival time. Urokinase-type plasminogen activator was selected as the single independent variable in the Cox model (p = 0.0001).

Background: Cysteine proteases (cathepsin B [CATB] and cathepsin L [CATL]), the serine protease urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI-1) are thought to play an important part in cancer invasion and metastasis. The aims of this study were to measure CATB, CATL, UPA, and PAI-1 in gastric cancer (GC) and normal mucosa distant from the tumor (NORM); to evaluate whether tissue levels are related to tumor stage, grade, or histotype; to assess their prognostic relevance; and to examine UPA and PAI-1 expression immunohistochemically., Methods: Gastric cancer and NORM samples were obtained from 25 patients with gastric cancer patients undergoing surgery (17 males, 8 females; mean age, 62 years; range, 31-84 years). Antigen concentrations were measured using the enzyme-linked immunosorbent assay method. Immunohistochemistry was performed using monoclonal UPA and PAI-1 antibodies., Results: Significantly higher antigen levels were found: (1) in GC vs. NORM (CATB, CATL, UPA, PAI-1) tissues; (2) in GC with versus without metastasis (CATB, CATL, UPA); (3) in poorly or moderately versus well differentiated GC; and (4) in diffuse versus intestinal-type GC (CATB, CATL). Urokinase-type plasminogen activator, PAI-1 and CATB levels had a significant prognostic impact. Cancer and stromal cells, showed immunoreactivity to anti-UPA and anti-PAI-1 antibodies., Conclusions: These results confirm the important role of CATB, CATL, UPA and PAI-1 in gastric cancer progression. Higher levels are detected in GC with metastases, poorer differentiation, and diffuse histotype, thus identifying patients with a worse prognosis.

Cathepsin B and cathepsin L--cysteine proteinases--may play an important role in cancer invasion and metastasis. The authors determined tissue antigen concentrations of cathepsins, using the ELISA method, in 25 patients with gastric cancer (17 males, 8 females, mean age 62, range 31-84). They evaluated the possible relationship that these proteinases may have with the presence of metastases, differentiation and histotype. Significantly higher cathepsin B and cathepsin L antigen levels were found: 1. in gastric cancer tissues vs. normal tissues distant from tumors (CATB: p < 0.05, CATL: p < 0.005); 2. in diffuse vs. intestinal type cancers (p < 0.05); 3. in patients with poorly vs. well-differentiated cancers (p < 0.05); in gastric cancers with vs. without metastasis (p < 0.05). Their results confirm that cathepsin B and L play an important role in gastric cancer invasion and metastasis. Considering the significantly higher cathepsins detected in cancers with metastasis, a poor differentiation and of diffuse histotype, these proteinases could be useful for identification gastric cancer patients with a poor prognosis.

Background: It has been proposed that the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) may play an important part in cancer spread and metastasis., Aims of the Study: 1. To determine the UPA, PAI-1 antigen levels in gastric cancer (GC) and in normal gastric mucosa far from the tumor (NORM). 2. To evaluate changes related to the presence of metastasis, tumor differentiation (grading) and histotype., Patients and Methods: Samples of tumor and of normal mucosa were obtained from 25 GC patients undergoing surgery (17 males, 8 females, mean age 62, range 31-84). Antigen concentrations were measured using the ELISA method., Results: Significantly higher UPA and PAI-1 antigen levels were found: 1. in GC vs. NORM tissue; 2. in patients with poorly and moderately differentiated GC vs. well-differentiated GC. UPA was significantly higher in GC with vs. without metastasis. PAI-1 was also higher, though not significantly so, in GC with metastasis than in GC without metastasis., Conclusion: Our results confirm that the serine protease UPA and its inhibitor PAI-1 play an important role in GC progression. Considering the higher protease levels detected in GC with metastases and poorer differentiation, UPA and PAI-1 might be useful for identifying gastric cancer patients with a poor prognosis.