Prognostic Significance of Ets-1 and the Matrix Metalloproteinase-2 to Tissue Inhibitor of Matrix Metalloproteinase-2 Ratio in Egyptian Epithelial Ovarian Cancer Patients

摘要

The invasive potential of epithelial ovarian cancer is the main factor determining its biological behavior. Ets-1 transcription factor is involved in the activation of several proteases participating in tumor invasion and metastasis. The balance of matrix metalloproteinase-2 and its inhibitor is important in the regulation of tumor invasion. This study included 31 tumors from patients with epithelial ovarian cancer in different stages, and 20 tissue samples from benign ovarian lesions as a control group. Ets-1 was assessed using immunohistochemistry. Matrix metalloproteinase-2 (MMP-2) and the MMP-2 inhibitor (TIMP-2) were measured in the cytosolic fractions using enzyme immunoassay. MMP-2 results were confirmed by gelatin zymography. ETS-1 was expressed only in the malignant group. MMP-2 and the MMP-2:TIMP-2 ratio were significantly higher in the malignant group (p=0.045 and 0.026, respectively) with significant correlation to stage and poor survival above the specified cut-off values (p=0.006 and 0.002, respectively). Log rank of Kaplan-Meier survival analysis was significant for FIGO stage, MMP-2 and the MMP-2:TIMP-2 ratio (p0.05). Multivariate analysis demonstrated that the MMP-2:TIMP-2 ratio is an independent prognostic parameter. Ets-1 could be a future target for therapeutic strategies. Moreover, the MMP-2:TIMP-2 ratio might serve as a new independent prognostic indicator of poor prognosis in epithelial ovarian cancer patients.