Elevated plasma tissue inhibitor of metalloproteinase‐1 levels predict decreased survival in castration‐resistant prostate cancer patients

BACKGROUND. Tissue inhibitor of metalloproteinase-1 (TIMP-1) has paradoxical multifunctional roles in tumorigenesis: inhibition of the catalytic activity of matrix metalloproteinases and apoptosis as well as promotion of angiogenesis and tumor growth. Elevated TIMP-1 levels have been associated with a poorer prognosis in multiple cancers. METHODS. Ethylenediaminetetraacetic acid plasma TIMP-1 was determined in 362 castration-resistant prostate cancer (PC) patients using a TIMP-1 enzyme-linked immunosorbent assay. All patients with castration-resistant PC and available plasma were identified from an institutional database. Overall survival was analyzed using the Kaplan-Meier method and Cox modeling on plasma TIMP-1 tertiles. RESULTS. Patients were evaluated in pilot (n = 60) and primary (n = 302) sets. Median follow-up from diagnosis was 5.8 and 6.6 years, respectively. Median plasma TIMP-1 levels were 335 and 183 ng/mL in the pilot and primary sets, respectively. Overall survival was significantly shorter with each higher tertile of TIMP-1 in both datasets (P 20 vs ≤20 ng/mL), alkaline phosphatase (>102 vs ≤102 U/L), Eastern Cooperative Oncology Group performance status (1 + vs 0), and Gleason score (7 or 8 vs ≤6). CONCLUSIONS. Elevated plasma TIMP-1 levels predicted decreased survival in metastatic castration-resistant PC patients, independent of known prognostic markers. Cancer 2011. © 2010 American Cancer Society.