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. 2010 Sep;136(9):1313-21.
doi: 10.1007/s00432-010-0782-2. Epub 2010 Feb 3.

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

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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

L O González et al. J Cancer Res Clin Oncol. 2010 Sep.

Abstract

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.

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Figures

Fig. 1
Fig. 1
Diagram showing the significant changes (p < 0.05) in MMPs/TIMPs expressions from pure DCIS to DCIS admixed with microinvasive foci, and to microinvasive foci
Fig. 2
Fig. 2
MMP-11 with low expression in pure DCIS (a) MMP-11 with high expression in DCIS wit microinvasive focus (b) 200×. MMP-13 with no expression in fibroblast in pure DCIS (c), MMP-13 with expression in fibroblast in DCIS with microinvasive focus 400× (d). TIMP-1 with no expression in inflammatory mononuclear cells in pure DCIS (e), TIMP-1 with expression in inflammatory mononuclear cells in DCIS with microinvasive focus (f) 400×

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