High MMP-1 mRNA Expression is a Risk Factor for Disease-Free and Overall Survivals in Patients with Invasive Breast Carcinoma

Abstract

Matrix metalloproteinase 1 (MMP-1) degrades extracellular matrix and thereby promotes tumor invasion and progression. In this study we examined the prognostic significance of tissue expression levels of MMP-1 mRNA in patients with invasive breast carcinoma. We assessed the prognostic value of MMP-1 mRNA expression in tumor tissue specimens from 85 breast carcinoma patients with a median follow-up time of 38 months (range, 2-48 months). MMP-1 mRNA levels were measured by real-time quantitative reverse transcriptase polymerase chain reaction (real time RT-PCR). The results were correlated with various clinicopathological parameters and clinical outcomes. mRNA expression levels of MMP-1 were higher in tumor tissue specimens than in adjacent normal breast tissue specimens from 15 patients (P < 0.023). MMP-1 mRNA levels showed no significant relationship with either tumor size or axillary node status but correlated inversely with estrogen receptor levels (P < 0.0043). High MMP-1 mRNA expression as determined by real-time RT-PCR correlated significantly with a high frequency of recurrence and fatal outcome (P < 0.025 and P < 0.020). Multivariate analysis using the Cox regression model indicated that high MMP-1 mRNA expression was an independent unfavorable prognostic factor (risk ratio, 6.37; P < 0.019). We have demonstrated for the first time the high mRNA expression of MMP-1 in patients whose carcinomas lack estrogen receptor expression. Our results suggest that MMP-1 is an important gene implicated in the progression of human breast cancer.