Abstract
BackgroundMatrix metalloproteinase 9 (MMP-9) is a type-IV collagenase that is highly expressed in breast cancer, but its exact role in tumor progression and metastasis is unclear.Methods MMP-9 mRNA and protein expression was examined by real-time reverse transcriptase PCR and immunohistochemical staining, respectively, in 41 breast cancer specimens with matched peritumoral benign breast epithelial tissue and suspicious metastatic axillary lymph nodes. Lymph vessels were labeled with D2-40 and lymphatic microvessel density (LMVD) was calculated. Correlation of MMP-9 protein expression with clinicopathological parameters and LMVD was also evaluated.ResultsMMP-9+ staining in breast cancer specimens (35/41, 85.4%) was higher than in matched epithelium (21/41, 51.2%; P<0.05) and lymph nodes (13/41, 31.7%; P<0.001). Higher MMP-9 mRNA expression was also detected in tumor specimens compared with matched epithelial tissues and lymph nodes (P<0.05). Elevated MMP-9 expression was correlated with lymph node metastasis and LMVD (P<0.05).ConclusionMMP-9 was overexpressed in breast cancer specimens compared with peritumoral benign breast epithelium and lymph nodes. Moreover, its expression in the matched epithelium and lymph nodes was positively associated with lymph node metastasis, and its expression in lymph nodes was positively associated with lymphangiogenesis in breast cancer. Thus, MMP-9 is a potential marker for breast cancer progression.
Highlights
Breast cancer is the most common tumor among women[1]and often metastasizes to the axillary lymph nodes
Matrix metalloproteinase-9 (MMP-9), known as gelatinase B, is a 92-kDa zinc-dependent endopeptidase that promotes degradation of type IV collagen, the main component of basement membrane[4].Interestingly, Matrix metalloproteinase 9 (MMP-9) is highly expressed in breast cancer, its expression is rarely associated with malignant factors[5,6].conflicting studies using experimental tumor systems reported correlations or lack thereof of increased MMP-9 expression with metastasis[7]
lymph vessel density (LMVD) assessment D2-40 is a commercially available mouse monoclonal antibody against human podoplanin, which is a mucin-type transmembrane protein in lymphatic endothelial cells[13].The antibody is a highly specific marker for lymphatic endothelium and has proven valuable in distinguishing lymph vessels from blood vessels and in detecting lymphatic invasion in various malignant neoplasms[11,14,15].In the present study, D2-40 staining was mainly detected in lymphatic endothelial cells, while tumor cells and blood vessels exhibited no staining (Figure 1B and 1C)
Summary
Breast cancer is the most common tumor among women[1]and often metastasizes to the axillary lymph nodes. Matrix metalloproteinase-9 (MMP-9), known as gelatinase B, is a 92-kDa zinc-dependent endopeptidase that promotes degradation of type IV collagen, the main component of basement membrane[4].Interestingly, MMP-9 is highly expressed in breast cancer, its expression is rarely associated with malignant factors[5,6].conflicting studies using experimental tumor systems reported correlations or lack thereof of increased MMP-9 expression with metastasis[7]. We undertook the present study to gain further insight into the expression pattern of MMP-9 in invasive breast cancer and its relationship with clinicopathological characteristics, lymph vessel density (LMVD), tumor metastasis potential and estrogen receptor (ER), progesterone receptor (PR), and HER2/neu status. Matrix metalloproteinase 9 (MMP-9) is a type-IV collagenase that is highly expressed in breast cancer, but its exact role in tumor progression and metastasis is unclear
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