Expression of metalloproteases and their inhibitors by tumor and stromal cells in ductal carcinoma in situ of the breast and their relationship with microinvasive events.

AIMS

This study aimed to investigate the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ (DCIS).

METHODS

We used inmunohistochemistry to compare the expression of MMPs and TIMPs in tumor or stromal cells for 50 pure DCIS and 12 DCIS with microinvasive foci.

RESULTS

Score values for collagenase-1 (MMP-1), membrane type 1 MMP (MMP-14), and TIMP-1, were significantly higher in pure DCIS than in DCIS with microinvasive foci, whereas stromalysin-3 (MMP-11) expression was significantly higher in DCIS with microinvasive foci. Both fibroblasts and mononuclear inflammatory cells (MICs) surrounding pure DCIS showed more frequently expression of MMP-1, MMP-14, and TIMP-3, whereas MMP-11 expression was more frequent in MICs of microinvasive tumors. MICs of microinvasive foci more frequently showed the expression of gelatinase A (MMP-2), MMP-11, collagenase-3 (MMP-13), and TIMP-1, than MICs surrounding pure DCIS; whereas peri-ductal MICs and fibroblasts from pure DCIS expressed TIMP-3 more commonly than these cells at microinvasive foci.

CONCLUSIONS

There are significant differences in the expression of MMPs and TIMPs, so in tumor cells and stromal cells, between pure DCIS and DCIS with microinvasive foci. Therefore, these staining patterns might display potential applications as biological markers, such as in evaluating microinvasion in resection specimens of breast tumors.