TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients

Sven Mahner,Fritz Jaenicke,Joerg Schwarz,Walter Carney,Linn Woelber,Christine Eulenburg,Karin Milde-Langosch,Volkmar Mueller

doi:10.1186/1471-2407-10-139

Abstract

BackgroundAngiogenesis appears to play an important role in ovarian cancer. Vascular endothelial growth factor (VEGF) has recently been implicated as a therapeutic target in ovarian cancer. The tissue inhibitor of metalloproteinase 1 (TIMP-1) is involved in tissue invasion and angiogenesis. The application of serum TIMP-1 and VEGF to monitor primary therapy and predict clinical outcome of patients with ovarian cancer is unclear.MethodsPatients with epithelial ovarian cancer who presented for primary surgery were included in this study. A total of 148 serum samples from 37 patients were analyzed. Samples were prospectively collected at 4 predefined time points: 1. before radical debulking surgery, 2. after surgery and before platinum/taxane based chemotherapy, 3. during chemotherapy, 4. after chemotherapy. Serum VEGF-165 and TIMP-1 as well as CA-125 were quantified by ELISA or ECLIA and correlation with response and long-term clinical outcome was analyzed.ResultsSerum levels of all markers changed substantially during first-line therapy. High CA-125 (p = 0.002), TIMP-1 (p = 0.007) and VEGF-165 (p = 0.02) after chemotherapy were associated with reduced overall survival. In addition, elevated CA-125 (p < 0.001) and VEGF-165 (p = 0.006) at this time point predicted poor progression-free survival. TIMP-1 and VEGF-165 were closely correlated at all time-points during therapy.ConclusionsTIMP-1 and VEGF serum levels changed significantly during first-line therapy of ovarian cancer patients and predicted prognosis. These findings support the role of angiogenesis in ovarian cancer progression and the use of antiangiogenic therapy.

Highlights

Angiogenesis appears to play an important role in ovarian cancer
According to a decrease in CA-125 serum concentrations, all patients responded to first-line treatment except for one
To investigate the role of new serologic biomarkers in therapy monitoring and to determine their potential prognostic significance in ovarian cancer, tissue inhibitor of metalloproteinase 1 (TIMP-1), Vascular endothelial growth factor (VEGF)-165 and CA-125 were analyzed in 148 serum samples from 37 patients with epithelial ovarian cancer

Summary

Introduction

Angiogenesis appears to play an important role in ovarian cancer. Vascular endothelial growth factor (VEGF) has recently been implicated as a therapeutic target in ovarian cancer. The tissue inhibitor of metalloproteinase 1 (TIMP-1) is involved in tissue invasion and angiogenesis. The application of serum TIMP-1 and VEGF to monitor primary therapy and predict clinical outcome of patients with ovarian cancer is unclear. Epithelial ovarian cancer accounts for the highest mortality among all gynecologic malignancies in the Western world. The American Cancer Society estimates more than 20.000 new cases and 15.000 deaths due to this disease each year in the United States [1]. Because of the absence of specific early symptoms most patients are diagnosed at an advanced stage with extensive intraabdominal disease and peritoneal carcinomatosis. Most patients will achieve radiologic and serologic complete remission after first-line therapy.

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