ABSTRACT
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Subject(s)
Breast Neoplasms/metabolism , Kaplan-Meier Estimate , Matrix Metalloproteinase 1/metabolism , RNA, Messenger/metabolism , Adult , Aged , Aged, 80 and over , Breast/cytology , Breast/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Disease Progression , Disease-Free Survival , Female , Follow-Up Studies , Humans , Matrix Metalloproteinase 1/genetics , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Prognosis , Proportional Hazards Models , RNA, Messenger/genetics , Receptors, Estrogen/metabolism , Risk FactorsABSTRACT
BACKGROUND: We examined expression patterns of matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in colorectal cancer tissues to assess their prognostic significance. MATERIALS AND METHODS: mRNA expressions of 17 MMPs, 4 TIMPs, and RECK were measured in 112 colorectal cancerous tissues, 20 normal mucosa tissues, and 11 metastatic liver lesions by real-time reverse-transcriptional-polymerase chain reaction. The protein level expressions were confirmed with immunohistochemistry. RESULTS: Cancers and normal mucosa displayed highly significant differences (P < 0.01) in expression of nine genes (MMP-1, -3, -7, -9, -10, -11, -12, -14, and RECK). Primary cancers and metastatic lesions showed highly significant differences (P < 0.01) in MMP-1, -10, -11, and TIMP-1. MMP-12 expression was higher in the primary tumors that were associated without hepatic metastasis than those with metastasis (P < 0.01). High expression of MMP-15 was related to longer disease-free survival (generalized Wilcoxon test, P < 0.0062; Cox hazard model, P < 0.028, hazard ratio, 0.099). CONCLUSIONS: MMP, TIMP, RECK expression patterns may provide an insight into extracellular matrix degrading (which is characteristic of colorectal cancers) and its role in metastasis.