Elevated plasma TIMP-1 levels predict reduced survival in metastatic hormone-refractory prostate cancer patients

Abstract

5143 Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to have parodoxical multifunctional roles in tumorigenesis: inhibition of the catalytic activity of MMPs, growth promotion, inhibition of apoptosis, and regulation of angiogenesis. Increased TIMP-1 has been associated with an unfavorable prognosis in many cancers including breast, colorectal, gastric, head and neck, lung cancer, and lymphomas. Methods: EDTA plasma TIMP-1 was determined from 60 hormone-refractory prostate cancer (HRCaP) patients using the TIMP-1 ELISA from Oncogene Science / Bayer HealthCare, Cambridge, MA. Patients were identified from an institutional database and had metastatic, HRCaP at the time of blood collection, which ranged from <1 month to 14 yrs. after the start of androgen-deprivation therapy (ADT); some patients had also received several chemotherapy regimens by the time of blood collection. Median follow-up was 17 mo. after blood collection and 27/60 patients had died. Overall survival was analyzed using Kaplan-Meier method and Cox modeling on tertiles of the TIMP-1 distribution. Results: The median EDTA plasma TIMP-1 level from the 60 HRCaP patients was 335 ng/ml (range 21 - 1391 ng/ml). Median survival since time of blood collection was 14 mo. Survival differed across TIMP-1 levels (P<0.01, logrank test), in particular the upper tertile of plasma TIMP-1 had a significantly reduced overall survival from the time of blood collection compared to the lowest tertile: A larger confirmatory study which will include a multivariate analysis of known prognostic factors is planned. Conclusions: Elevated plasma TIMP-1 tertile level predicted reduced survival in HRCaP patients. Soluble TIMP-1 deserves further study to determine its predictive and prognostic biomarker potential in a larger cohort of prostate cancer patients. [Table: see text] [Table: see text]