Research article

Tumor-derived matrix metalloproteinase-13 (MMP-13) correlates with poor prognosis of invasive breast cancer

Bin Zhang^{* 1,2} , Xuchen Cao^{* 1,2} , Yanxue Liu³ , Wenfeng Cao³ , Fei Zhang¹ , Shiwu Zhang³ , Hongtao Li^1,2 , Liansheng Ning^1,2 , Li Fu^1,4 , Yun Niu^1,4 , Ruifang Niu¹ , Baocun Sun^1,3 and Xishan Hao¹

¹National Key Laboratory of Breast Cancer Prevention and Treatment, Tianjin Medical University Cancer Institute and Hospital (TJMUCIH), Tianjin, P.R.CHINA

²Department of Breast Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital (TJMUCIH), Tianjin, P.R.CHINA

³Department of Pathology, Tianjin Medical University Cancer Institute and Hospital (TJMUCIH), Tianjin, P.R.CHINA

⁴Department of Breast Cancer Pathology, Tianjin Medical University Cancer Institute and Hospital (TJMUCIH), Tianjin, P.R.CHINA

author email corresponding author email* Contributed equally

BMC Cancer 2008, 8:83doi:10.1186/1471-2407-8-83

Published:	28 March 2008

Abstract

Background

Experimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression, however, its role is yet to be fully 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).

Methods

Immunohistochemistry (IHC) was performed on paraffin-embedded tissue microarray specimens from 263 breast carcinomas. The intensity and the extent of IHC were scored by pathologists. The correlation of the gene expression profiles with the patients' clinicopathological features and clinical outcomes were analyzed for statistical significance.

Results

MMP-13 protein was detected in the cytoplasm of malignant cells and 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.

Conclusion

Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes, and inversely correlated with 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.