Tumor-derived matrix metalloproteinase-13 (MMP-13) correlates with poor prognoses of invasive breast cancer.
BACKGROUND
Experimental 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).


METHODS
Immunohistochemistry (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.


RESULTS
MMP-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.


CONCLUSIONS
Tumor-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.
Zhang
Bin
B
National Key Laboratory of Breast Cancer Prevention and Treatment, Tianjin Medical University Cancer Institute and Hospital (TJMUCIH), Tianjin, PR China. eeflying@163.com
Cao
Xuchen
X
Liu
Yanxue
Y
Cao
Wenfeng
W
Zhang
Fei
F
Zhang
Shiwu
S
Li
Hongtao
H
Ning
Liansheng
L
Fu
Li
L
Niu
Yun
Y
Niu
Ruifang
R
Sun
Baocun
B
Hao
Xishan
X
D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D003593:Cytoplasm / Q000201:enzymology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017154:Stromal Cells / Q000201:enzymology; D015996:Survival Rate; D014018:Tissue Distribution; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D018719:Erb-b2 Receptor Tyrosine Kinases; D019714:Tissue Inhibitor of Metalloproteinases