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


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.
Span
Paul N
PN
Department of Chemical Endocrinology, University Medical Center Nijmegen, The Netherlands. p.span@ace.umcn.nl
Sweep
C G J
CG
Manders
Peggy
P
Beex
Louk V A M
LV
Leppert
David
D
Lindberg
Raija L P
RL
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D053504:Matrix Metalloproteinases, Membrane-Associated; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; C115460:RECK protein, human; D012333:RNA, Messenger; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases