Prognostic Significance of Matrix Metalloproteinase-9 (MMP-9) in Epithelial Ovarian Cancer

Objective: We investigated the expression of matrix metalloproteinase-9 (MMP-9) and its relation to clinicopathologic factors and survival and also to previously analyzed expressions of CD44 and hyaluronan in epithelial ovarian cancer.

Methods: The expression of MMP-9 was analyzed immunohistochemically in 292 primary tumors and their 31 metastases.

Results: A low proportion of strong MMP-9 expression in cancer cells and high stromal MMP-9 expression correlated with advanced stage of the tumor (p=0.003, p=0.02, respectively). Stromal MMP-9 expression significantly correlated with hyaluronan positivity (p<0.0005), whereas MMP-9 did not correlate with CD44. In univariate analysis, a longer 10-year disease-related survival (DRS) was found in patients with a high proportion of MMP-9 or strong MMP-9 expression in cancer cells (p=0.02, p=0.05, respectively). However, high stromal expression of MMP-9 indicated short DRS (p=0.01). In multivariate analysis of all patients, MMP-9 expressing cancer or stromal cells were not independent prognostic factors, while in FIGO stage I patients a high percentage of MMP-9 positive cancer cells was associated with long DRS (p=0.008).

Conclusion: These data suggest that MMP-9 has a dual role in tumor progression, acting against tumor advancement when in tumor epithelium and promoting tumor progression while in the stroma.