Gelatinases and their tissue inhibitors in ovarian tumors; TIMP-1 is a predictive as well as a prognostic factor

Abstract

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.

Conclusion: We conclude that an elevated preoperative serum TIMP-1 concentration correlates to the aggressive behavior of ovarian cancer.