Gelatinases and their tissue inhibitors in ovarian tumors; TIMP-1 is a predictive as well as a prognostic factor.
OBJECTIVE
In the present study, the significance of circulating matrix metalloproteinases -2 and -9 (MMP-2, MMP-9), as well as their tissue inhibitors -1 and -2 (TIMP-1, TIMP-2) in ovarian cancer were studied to assess the possibility of using them in clinical decision-making.


METHODS
We measured, prior to primary surgery, the concentrations of these proteins in serum samples of 115 patients with an ovarian tumor: 63 with cancer, 6 with a low malignant potential tumor, and 46 with a benign tumor. The measurements were performed with enzyme-linked immunosorbent assays (ELISA). The results were compared to clinicopathological data.


RESULTS
A high serum concentration of TIMP-1 at diagnosis was found to correlate with the malignant phenotype of an ovarian tumor. Within malignant neoplasias, high circulating TIMP-1 correlated to the aggressive phenotype and unfavorable prognosis. An association was found between a high serum level of TIMP-1 and an advanced stage of the disease, a residual tumor>2 cm, poor response to cytotoxic treatment, shorter recurrence free time, and shorter cancer-related overall survival. No statistically significant correlation was found between the circulating gelatinases (MMP-2, MMP-9) or TIMP-2 and the clinicopathological factors. However, a tendency for better survival with high serum concentration of TIMP-2 or MMP-2 was observed.


CONCLUSIONS
We conclude that an elevated preoperative serum TIMP-1 concentration correlates to the aggressive behavior of ovarian cancer.
Rauvala
M
M
Department of Obstetrics and Gynecology, The University Hospital of Oulu, PL 24, Fin-90029 OYS, Oulu, Finland. marita.rauvala@oulu.fi
Puistola
U
U
Turpeenniemi-Hujanen
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9