Prognostic significance of stromal metalloproteinase-2 in ovarian adenocarcinoma and its relation to carcinoma progression

OBJECTIVES: MMP-2 expression in ovarian cancer cells has been correlated with poor prognosis. This study attempts to assess the prognostic importance of stromal MMP-2 in patients with ovarian endometrioid and serous adenocarcinoma. METHODS: MMP-2, MMP-2 activator, MT1-MMP, and its inhibitor (TIMP-2) were immunostained in 84 primary epithelial ovarian carcinomas (EOCs) (35 endometrioid adenocarcinomas ECs] and 49 serous adenocarcinomas SCs]). Results were correlated to pathological subtypes, tumor stage, grade, size, and to recurrence-free and cancer-specific survival. RESULTS: MMP-2 and stromal MMP-2 were detected in all carcinoma cells of 22.2% of EC and 77.8% of SC tumors. MT1-MMP co-localized with MMP-2. TIMP-2 staining was weak and cytoplasmically distributed in all tumors. Univariant analysis showed expression of stromal MMP-2 significantly associated with advanced stage (P = 0.018), higher grade (P = 0.005), serous subtype (P = 0.02), smaller tumor size at operation (P = 0.001), and higher incidence of recurrence (P = 0.042), but not with the rate of death due to cancer. By multiple Cox proportional hazard regression analysis, patient survival and disease-free survival were significantly related to the presence of stromal MMP-2 in EC but not SC patients (P < 0.05). However, after multivariant analysis, the associations with patient age, tumor stage, grade, and size no longer existed. In stepwise selection, tumor stage remained the most important predictor of patient survival and disease-free survival in ovarian EC and SC, but stromal MMP-2 remained the most important predictor of recurrence-free survival in patients with EC. CONCLUSIONS: Stromal MMP-2 occurs early and may play a role early in EOC invasion. Tumor stage and stromal MMP-2 are important predictors of disease-free survival.