Prognostic significance of the combined expression of matrix metalloproteinase-9, urokinase type plasminogen activator and its receptor in breast cancer as measured by Northern blot analysis

Using Northern blot analysis we have measured the co-expression of the matr ix metalloprotease MMP-9, plasminogen activator urokinase type (uPA) and it s receptor (uPAR) mRNAs in 81 biopsies of breast carcinomas with the object ive of analyzing the impact of these factors on the overall survival probab ility of the patients (median follow-up time: 4 years). Individual mRNA lev els of either uPA or uPAR showed parallel variations with MMP-9 mRNA, sugge sting a coordinate transcription of these markers. When median values were used as cutoff points to discriminate between high and low factor expressio n, no association was found with patient outcome and MMP-9 or uPA mRNA dist ribution. However, increased uPAR mRNA levels were associated with poor pro gnosis (p = 0.01). The combination of MMP-9 and uPAR mRNA measurements has not enhanced prognostic information compared to information supplied by the receptor alone (p = 0.01). The combination of MMP-9 and high levels of uPA mRNA led to a significant association with poor outcome (p = 0.03). Multiv ariate analysis supported the notion that increased uPAR mRNA production in primary breast cancer may be a predictor of overall survival.