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.

Prognostic significance of E-cadherin-catenin complex in epithelial ovarian cancer.

OBJECTIVE: To clarify the prognostic role of E-cadherin and beta- and gamma-catenins, and their relation to CD44 in epithelial ovarian carcinoma. METHODS: The expression of E-cadherin and beta- and gamma-catenins was analysed immunohistochemically in 305 primary epithelial ovarian cancers and 44 metastases, and related to CD44 expression, clinicopathological factors, and the patients' survival. RESULTS: Reduced cell surface expression of E-cadherin, beta-catenin, and gamma-catenin was particularly frequent in serous and endometrioid histological types. Reduced cell surface expression of E-cadherin and beta-catenin was also associated with poor differentiation. Nuclear positivity of beta-catenin was associated with high CD44 expression, endometrioid histology, and local stage of the tumour, whereas nuclear gamma-catenin expression was associated with serous histology and poor differentiation. In the univariate analysis, preserved cell surface beta-catenin expression in the whole study material and nuclear expression of beta- and gamma-catenins in the subgroup of endometrioid ovarian cancers were predictors of better 10 year disease related survival. Preserved cell surface expression of E-cadherin and beta-catenin predicted favourable recurrence-free survival. These statistical significances were not retained in multivariate analysis. CONCLUSIONS: The correlation between nuclear beta-catenin and CD44 indicates that beta-catenin may regulate the transcription of CD44 in epithelial ovarian cancer. E-cadherin-catenin complex members are associated with the prognosis of patients with epithelial ovarian cancer, but these univariate associations were not strong enough to compete for significance with the traditional clinicopathological factors.