Abstract
Abstract Body: Background: Matrix metalloproteinases (MMPs) play a key role in invasion and metastasis of cancer cells. MMPs are able to degrade extracellular matrix and aid formation of new blood vessels, thus supporting metastatic tumor growth and angiogenesis. The MMP family can be regulated by their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs), which bind MMPs noncovalently. TIMP-1 has paradoxical multifunctional roles in tumorigenesis, independent of its original MMP-inhibitory role: growth promotion, inhibition of apoptosis, and regulation of angiogenesis. Overexpression of TIMP-1 confers resistance to chemotherapy in cell culture, and increased TIMP-1 has been associated with an unfavorable prognosis in multiple cancer types. TIMP-1 has recently been reported to be a predictive biomarker in large human breast cancer trials. The purpose of this study was to determine the correlation between serum TIMP-1 levels at the time of diagnosis in patients with ovarian cancer and correlate this biomarker with overall survival. Methods: Serum TIMP-1 was assayed from 36 patients diagnosed with ovarian cancer between 1982 and 1987. Blood was collected at the time of diagnosis and serum frozen. Serum TIMP-1 levels were measured using a TIMP-1 ELISA from Oncogene Science / Siemens Healthcare Diagnostics (Cambridge, MA). Clinical outcome data were correlated with serum TIMP1 levels. Results: TIMP-1 levels from 36 patients had a mean of 559 ng/ml with SD of + 296 (range 145 to 1460 ng/ml). 35 of 36 patients had clinical follow up data available. 82.14% of patients had distant metastasis, 7.14 % had localized tumor, and 10.71 % had regional involvement. Elevated serum TIMP-1 level predicted shorter survival in ovarian cancer by quartile analysis (p=0.022). Median survival was 4079 days for patients with the lowest serum TIMP-1 quartile, and 106 days for those with the highest serum TIMP-1 quartile. On a continuous basis, higher serum TIMP-1 trended to predict significant shorter survival (p=0.063). Conclusions: Elevated serum TIMP-1 levels at the time of diagnosis predicted shorter survival in ovarian cancer. Circulating TIMP-1 deserves further study as a predictive and prognostic factor in ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4651.
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