Matrix metalloproteinase inhibitor reversion-inducing cysteine-rich protein with Kazal motifs: A prognostic marker for good clinical outcome in human breast carcinoma

• Published in: Cancer 2003-06, Vol.97 (11), p.2710-2715
• Main Authors: SPAN, Paul N, SWEEP, C. G. J, MANDERS, Peggy, BEEX, Louk V. A. M, LEPPERT, David, LINDBERG, Raija L. P
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarkers, Tumor - analysis; Breast Neoplasms - chemistry; Breast Neoplasms - mortality; Breast Neoplasms - therapy; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic - physiology; GPI-Linked Proteins; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases, Membrane-Associated; Medical sciences; Membrane Glycoproteins - analysis; Membrane Glycoproteins - genetics; Metalloendopeptidases - antagonists & inhibitors; Middle Aged; Polymerase Chain Reaction; Prognosis; Regression Analysis; RNA, Messenger - analysis; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.11395

The recently described reversion-inducing cysteine-rich protein with Kazal 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. 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. 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). 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.