title: Increased serum 72 KDa metalloproteinase in serous ovarian tumors: comparison with CA 125.
abstract: 72 KDa metalloproteinase (MMP-2) is an enzyme present in neoplastic cells and also in normal fibroblasts. It specifically cleaves type IV collagen, and therefore may play a critical role in tumor invasion and metastasis mechanisms. The aim of the present study was to determine serum levels of MMP-2 in serous ovarian tumors, and compare these with serum levels of CA 125. Ten primary ovarian serous cystadenocarcinomas, 5 borderline tumors, and 10 serous cystadenomas, all treated with primary surgery, were recruited from our series of serous ovarian tumors, and studied. Patients' serum samples were obtained before surgery, and the MMP-2 levels were measured by the substrate capture enzyme-linked immunosorbet assay. The analysis of serum MMP-2, gave values significantly higher in cystadenocarcinomas than in borderline tumors and cystadenomas (one way analysis of variance, P < 0.001); in particular, serum MMP-2 was significantly correlated to the MMP-2 immunostaining of the tumor (Spearman correlation, r = 0.82, and P < 0.001). An arbitrary cutoff of the median value of normal adult female samples (0.22 units) was chosen, and all except for one patient with cystadenocarcinoma was shown to have serum MMP-2 levels above the cutoff value, with 90% sensitivity, 70% specificity, and a 75% positive predictive value (50% of Cohen's Kappa); on the other hand, CA 125 showed 80% sensitivity, and a 73% positive predictive value. The association of serum MMP-2 with CA 125 increased sensitivity to 100% in patients with cystadenocarcinoma, with 70% persisting specificity and a 77% positive predictive value (54% of Cohen's Kappa). Serum MMP-2 levels were found to be significantly increased in patients with cystadenocarcinoma in comparison with borderline tumors and cystadenomas, showing a direct relationship with tissutal MMP-2 expression in serous ovarian tumors. Although our results were preliminary, they clearly suggested that serum MMP-2 may be an interesting diagnostic marker for cystadenocarcinomas.
authors.affiliation: Institute of Obstetrics and Gynecology, University of Ancona, Italy.
authors.forename: G G
authors.initials: GG
authors.lastname: Garzetti
authors.forename: A
authors.initials: A
authors.lastname: Ciavattini
authors.forename: G
authors.initials: G
authors.lastname: Lucarini
authors.forename: G
authors.initials: G
authors.lastname: Goteri
authors.forename: C
authors.initials: C
authors.lastname: Romanini
authors.forename: G
authors.initials: G
authors.lastname: Biagini
mesh_terms: D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D018284:Cystadenocarcinoma, Serous / Q000097:blood* / Q000473:pathology / Q000601:surgery; D018293:Cystadenoma, Serous / Q000097:blood* / Q000473:pathology / Q000601:surgery; D005260:Female; D018093:Gelatinases / Q000032:analysis* / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000032:analysis* / Q000097:blood*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D012016:Reference Values; D012044:Regression Analysis
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2