High Serum TIMP-1 is Associated with Adverse Prognosis in Endometrial Carcinoma

Abstract

Background: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a key role in extracellular matrix (ECM) turnover and remodeling. Changes in their expression levels have been observed in various tumor types. However, their clinical significance and prognostic importance in the progression of endometrial carcinoma is still unclear. This study aimed to evaluate the circulating levels of gelatinases and tissue inhibitors of gelatinases, and to study their relationships with the clinical behavior of endometrial cancer. Materials and Methods: Pretreatment serum levels of MMP-2, MMP-9, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were quantitatively measured by enzyme-linked immunosorbent assay (ELISA) in 93 patients presenting with primary endometrioid endometrial adenocarcinoma. The study population was divided into low-risk and high-risk patient groups as determined by conventional prognostic criteria. Results: Elevated serum levels of TIMP-1 at diagnosis were found in the high-risk patient group (p=0.018). The median follow-up time was 101 months. A cut-off value of 536 ng/ml was used to divide the serum values of TIMP-1 into two groups. A high serum concentration of TIMP-1 was associated with shortened relapse-free (p=0.036) and cancer-specific survival (p=0.029). Conclusion: The results suggest that the preoperative serum TIMP-1 level predicts the behavior of endometrial cancer. However, in multivariate analysis TIMP-1 was not an independent prognostic factor.