Gelatinase A-immunoreactive protein in ovarian lesions- prognostic value in epithelial ovarian cancer.

Objective: Gelatinase A (MMP-2) is a member of the matrix metalloproteinase family and it degrades the major component of the basement membrane, type IV collagen. MMP-2 has been linked to invasion in different types of cancer.

Method: We have studied the localization of MMP-2 in 18 benign, 3 borderline, and 33 malignant ovarian lesions by immunohistochemical stainings using a monoclonal antibody against MMP-2.

Results: MMP-2-immunoreactive protein was localized in epithelial cells and in fibroblasts. Two types of cytoplasmic staining were observed, a diffuse and a granular pattern. The diffuse staining model was found more often. In 19% of the cases, both staining patterns were present in epithelial cells. Granular staining was found in epithelial cells in cystadenomas and in ovarian cancer cells. The pattern of MMP-2 positivity in fibroblasts was diffuse. MMP-2 positivity in cancer cells was associated with recurrent disease (P < 0.05) in ovarian cancers. MMP-2 negativity in fibroblasts correlated to Grade 3 (P < 0.01), Stage III-IV (P < 0.001), recurrency (P < 0.05), and refractory disease (P < 0.05) in ovarian cancer. The relative survival rate was 32% in patients with an MMP-2-positive ovarian cancer, 57% in patients with an MMP-2-negative ovarian cancer, and 19% in patients with MMP-2 positivity in cancer cells and concomitant negativity in stromal fibroblasts. The disease-free 5-year survival rates were 25, 57, and 12.5%, respectively.

Conclusions: These data suggest that MMP-2 may contribute to poor prognosis of ovarian cancer.