Matrix metalloproteinase inhibitor reversion‐inducing cysteine‐rich protein with Kazal motifs

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Abstract
BACKGROUND: The recently describedreversion‐inducingcysteine‐rich protein withKazal motifs (RECK) inhibits membrane Type 1 matrix metalloproteinase (MMP‐14), MMP‐2, and MMP‐9 secretion and enzymatic activity. Its expression is essential for normal vasculogenesis. Down‐regulation of RECK has been implicated in tumor angiogenesis and progression.METHODS: The authors assessed the prognostic value of RECK expression in tumor tissue specimens from 278 breast carcinoma patients with a median follow‐up time of 75 months (range, 2–169 months). RECK mRNA levels were measured by real‐time quantitative reverse transcriptase–polymerase chain reaction.RESULTS: Expression levels of RECK were lower in tumor tissue specimens than in adjacent normal breast tissue specimens from 10 patients (P= 0.028). No relevant associations of RECK with established clinicopathologic factors or treatment regimens were found. RECK expression predicted a longer recurrence‐free survival time (RFS;P= 0.037) at the optimal cutoff value (hazard ratio, 0.66; 95% confidence interval, 0.44–0.98). The 100 patients whose tumors exhibited low levels of RECK had a mean RFS time of 80.4 months and a 61.8% 5‐year RFS rate, whereas the 178 patients with tumors with high RECK expression had a mean RFS time of 91.2 months and a 73.0% 5‐year RFS rate. Multivariate Cox regression analysis showed that RECK expression maintained a significant independent prognostic value for RFS time (P= 0.047).CONCLUSIONS: These results are in agreement with the notion of RECK being an important tumor‐suppressor gene. Therefore, the possibility of applying RECK, a pharmaceutical mimetic, or drugs activating endogenous RECK expression, as possible therapeutic or preventive agents for breast carcinoma should be explored. Cancer 2003;97:2710–5. © 2003 American Cancer Society.DOI 10.1002/cncr.11395