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. MTI-MMP colocalized 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), highergrade (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. (C) 2003 Elsevier Inc. All rights reserved