Cellular protein and mRNA expression patterns of matrix metalloproteinases-2, -3 and -9 in human breast cancer: correlation with tumour growth.

The expression of matrix metalloproteinases (MMPs) with type IV collagenase activity has been associated with tumour invasion and metastatic potential in experimental models. We studied whether the cellular localization of MMP expression provides useful information on tumour behaviour in human breast cancer. Immunohistochemistry and non-radioisotopic-detected in situ hybridization were used to study protein and mRNA expression profiles for MMPs-2, -3 and -9 in paraffin sections of 70 invasive breast carcinomas. Protein and mRNA expression of the MMPs was observed in tumour as well as in peritumoural stromal cells. MMP protein expression was increased at the invasive border (p < 0.05). Grade 3 carcinomas expressed MMP-2 mRNA in significantly more tumour cells than grade 2 carcinomas (p = 0.006). Ductal carcinomas with an extensive intraductal component were characterized by the lowest percentages of MMPs-2 and -3 mRNA expressing peritumoural stromal cells (p < 0.05). No correlation was observed between MMP protein/mRNA expression and pTNM classification. In conclusion our results indicate that the expression of MMPs is associated with tumour behaviour. The correlation of MMPs-2 and -3 expression in peritumoural stromal cells with tumour type, shown for the first time, suggests that transcriptional regulation of these MMPs in stromal cells is important for the growth pattern of breast cancer.