Abstract
BackgroundExperimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression. However, its relevance to the progression of human breast cancer is yet to be established. Furthermore, it is not clear whether MMP-13 can be used as an independent breast cancer biomarker. This study was conducted to assess the expression profile of MMP-13 protein in invasive breast carcinomas to determine its diagnostic and prognostic significance, as well as its correlation with other biomarkers including estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, MMP-2, MMP-9, tissue inhibitor of MMP-1 and -2 (TIMP-1 and TIMP-2).MethodsImmunohistochemistry (IHC) was performed on paraffin-embedded tissue microarray containing specimens from 263 breast carcinomas. The intensity and the extent of IHC were scored by pathologists in blind fashion. The correlation of the gene expression profiles with patients' clinicopathological features and clinical outcomes were analyzed for statistical significance.ResultsMMP-13 protein was detected in the cytoplasm of the malignant cells and the peritumoral stromal cells. MMP-13 expression by tumor cells (p < 0.001) and stromal fibroblasts (p <0.001) both correlated with carcinoma infiltration of lymph nodes. MMP-13 also correlated with the expression of Her-2/neu (p = 0.015) and TIMP-1 (p < 0.010), respectively in tumor cells. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes. Moreover, high levels of MMP-13 expression were associated with decreased overall survival. In parallel, the prognostic value of MMP-13 expressed by peritumoral fibroblasts seems less significant. Our data suggest that lymph node status, tumor size, Her-2/neu expression, TIMP-1 and MMP-13 expression in cancer cells are independent prognostic factors.ConclusionTumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes, and inversely correlated with the overall survival of breast cancer patients. MMP-13 may serve as an independent prognostic factor for invasive breast cancer patients. MMP-13 may be particularly useful as a prognostic marker when evaluated along with Her-2/neu and lymph node status.
Highlights
Experimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression
Further studies are needed to clarify whether MMP-13 and tissue inhibitor of matrix metalloproteinase (TIMP) act as cognate partners or independent of each other. This IHC study of Tissue mcroarrays (TMA) with 263 specimens of Chinese breast cancer provided the first evidence that MMP-13 is highly expressed by both the tumor cells and adjacent fibroblast cells
Our study suggests a potential application of MMP-13 as an independent biomarker for breast cancer prognosis
Summary
Experimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression. The incidence and mortality rate of breast cancer increased sharply in China over the last couple of decades [1] Clinical parameters, such as the size of the primary tumor, the histological grade, and regional lymph node involvement, are generally useful for predicting the prognosis. In light of the racial disparities of breast cancer incidences and prognoses documented in the literature, it is important to identify and validate specific biomarkers for Chinese breast cancer patients. To this end, estrogen receptor (ER)/progesterone receptor (PR), and oncogene Her-2/ neu have been shown to be useful markers of breast cancer [2,3]
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