Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera

Matrix metalloproteinases, in particular the gelatinases MMP-2 and MMP-9, have received great attention in recent years as putative tumour markers for clinical applications. The main reason for the observed interest is their easy detection in body fluids. Moreover, recent evidence has shown multiple functions of MMPs, rather than simply degrading ECM, which include the mobilisation of growth factors and processing of surface molecules. Several authors have reported increased levels of MMPs in a number of cancers, but clinical correlations in breast cancer are still fragmentary. Thus, the aim of the present research was to investigate the activity levels of circulating gelatinases in the sera of breast cancer patients by means of zymographic analysis, and correlate data with clinicopathological parameters. In all, 80 patients and 22 healthy volunteers were involved in this study. Sera were obtained prior to surgery. The clinical variables were: grading of tumours, tumour size, lymph node involvement, tumour staging, oestrogen and progesterone receptor levels (76 out of 80 cases), and c-erbB-2 levels (46 cases). The densitometric measures of MMP-2 and MMP-9 activity levels indicated that the average values of both gelatinase activities were significantly higher in breast cancers than in control sera (P<0.0001). In addition, our analysis showed for the first time that elevated activity levels of both gelatinases correlated only with c-erbB-2 overexpression (P = 0.0273 for MMP-2 and P = 0.0075 for MMP-9). An inverse correlation was observed with regard to oestrogen receptor expression (P = 0.0075 for MMP-2 and P = 0.0273 for MMP-9). Moreover, a borderline inverse correlation was observed between the activity levels of both enzymes and nuclear grade (P = 0.0511 for MMP-2 and P = 0.0794 for MMP-9). In conclusion, the present data suggest that serum measures of MMP's activity may have diagnostic value for discriminating subgroups of breast cancer patients and support the hypothesis that ERBB2 amplification and/or overexpression enhance signalling pathways that may lead to increased production of gelatinases in c-erbB-2 positive breast cancers with higher metastatic potentialities.