High MMP-1 mRNA expression is a risk factor for disease-free and overall survivals in patients with invasive breast carcinoma.
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.


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.
Division of Cancer-Related Genes, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Shaoqiang
S
Cheng
Mitsuhiro
M
Tada
Yasuhiro
Y
Hida
Toshimichi
T
Asano
Taro
T
Kuramae
Norihiro
N
Takemoto
Jun-Ichi
J
Hamada
Masaki
M
Miyamoto
Satoshi
S
Hirano
Satoshi
S
Kondo
Tetsuya
T
Moriuchi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D020781:Matrix Metalloproteinase 1