[Elevated expression of matrix metalloproteinase-9, and fibronectin concentration in recurrent epithelial ovarian...

Ovarian cancer is the leading cause of mortality from gynecologic malignancies in developed countries. However, the outcome of apparently similar cases with regard to histology and stage is highly variable. In contrast to carcinomas of parenchymal organs such as the breast, lung, and colon, the spread of the epithelial ovarian carcinomas is characterized by transcoelomic dissemination of tumor cells into the peritoneal cavity. Matrix metalloproteinases, and fibronectin play an important role in this process.

The authors made an attempt to predict recurrence of ovarian cancer by comparing the clinico-pathologic characteristics, grading and biological behavior of the ovarian malignancies with the matrix metalloproteases activities and fibronectin expression. This study involved 17 patients with epithelial ovarian cancers, 5 patients with benign ovarian tumours, 5 patients with normal ovaries, 5 patients with ovarian tumours of low malignant potential, 4 patients with sex-cord stromal ovarian tumours and 2 patients with germ cell ovarian tumours. Matriolytic activity was detected in the surgically removed tumours, in serum and in ascites by gelatin zymography and quantitative assessment was performed by using densitometric scanning wih an Eagle Eye II (Stratagenic CA. USA). MMP-2 and MMP-9 activity was expressed in arbitrary units (U) per 10 g of ovarian cancer tissue. Fibronectin content was identified by Western blot analysis and quantity estimated by densitometric analysis. The-median follow-up period was 20.5 months.

Activated forms of matrix metalloproteinase-2,-and-9 were not detected in normal ovaries. The expression levels of MMP-2 and MMP-9 were higher in epithelial ovarian cancers than in benign ovarian tumors, but the differences were not statistically significant. The MMP-9 activity was markedly elevated in advanced-stage and poorly-differentiated ovarian cancer compared to early-stage and well-differentiated ovarian malignancy. This relationship was not observed with regard to MMP-2 activity. The fibronectin concentration was significantly higher in ovarian cancers compared with benign ovarian tumors and normal ovaries. Fibronectin concentration significantly elevated in ovarian cancer patients with recurrent disease compared with ovarian cancer patients without recurrence. In patients with recurrent ovarian cancer the activated forms of MMP-9 were significantly higher compared to ovarian cancers without recurrence.

In conclusion, our data support the hypothesis that the expression of tumor-derived matriolytic enzymes and fibronectin are important in the growth of ovarian tumours. The interaction of MMP-9 with fibronectin appears to be one of the key factors in the biology of epithelial ovarian cancers.