Expression of matrix metalloproteinases and related tissue inhibitors in the cyst fluids of ovarian mucinous neoplasms

Objectives and methods. The growth of an ovarian cystic neoplasm often invo lves its invasion into and destruction of the extracellular matrix. We exam ined neoplastic cysts of ovarian mucinous tumors for the presence of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) using zymo graphy (in situ zymography, gelatin zymography, and casein zymography) and enzyme-linked immunosorbent assay. Results. Matriolytic activity was detected within the cystic contents and c ytoplasm of the lining epithelial cells of the cyst by in situ zymography. This intracystic matriolytic activity was thought to originate mainly in th e epithelial cells. The activated form of MMP-9 was: seen in all carcinoma and borderline fluids and in 7 of 15 adenomas. The concentration of MMP-9 w as higher in carcinoma fluids than in borderline and adenoma fluids (P < 0. 05). TIMP-1, which specifically binds to MMP-9, was also higher in carcinom a and borderline fluids than in adenoma fluids (P < 0.05). MMP-2 activity w as nearly ubiquitously present in all cyst fluids, irrespective of the flui d's histologic category. The amount of MMP-2 was highest in the carcinoma c ategory, although not to a statistically significant degree. TIMP-2, a spec ific inhibitor for MMP-2, was significantly lower in the borderline categor y than in the adenoma category. The molar ratios of TIMP-1/MMP-9 (not signi ficant) and TIMP-2/MMP-2 (P < 0.05) were higher in the adenoma category. Ex pressions of trypsin, MMP-7, and MMP-9 were generally higher in carcinoma a nd borderline fluids than in adenoma fluids. Conclusions. These observations indicate the importance of ovarian cystic f luids for analyzing tumor-associated matriolytic activities. The findings s uggest that these matriolytic enzymes, together with the presence of their inhibitors, play an important role in the growth of ovarian mucinous tumors . (C) 2000 Academic Press.