[Relationship between the expression of matrix metalloproteinase-13 protein and other biomarkers, prognosis in invasive breast cancer].
OBJECTIVE
The study was designed to investigate the expression patterns of metalloproteinase (MMP)-13 protein in invasive breast carcinoma and to determine the clinicopathological and prognostic values of its various localization and relation to the tumor phenotypes.


METHODS
Immunohistochemistry was performed on paraffin-embedded tissue array from 263 invasive breast carcinomas to investigate the protein expressions of MMP-13, estrogen receptor, progesterone receptor, HER2, MMP-2, MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1, TIMP-2.


RESULTS
MMP-13 protein was detected in the cytoplasm of carcinoma cells and peritumoral fibroblasts. High level expression of MMP-13 protein in tumor cells was associated with more lymph node involvement and higher tumor grade (both P < 0.01), and positively correlated with HER2 (P = 0.015) and TIMP-1 protein (P < 0.01) expression in carcinoma cells. Moreover, high expression of MMP-13 was associated with shortened overall survival for the entire patient population and the patient group with positive lymph node. Tumor cell derived MMP-13 had different impact on patients with different HER2 status. Peritumoral fibroblasts derived MMP-13 protein, although correlated with tumor cell derived MMP-13 and associated with lymph node stage and HER2 expression, was found having less prognostic impact. Univariate survival analysis showed that the tumor size, grade, lymph node status, PR status, HER2 expression, tumors TIMP-1 and MMP-13 expression were prognostic factors. However, multivariate survival analysis showed that only tumor size, lymph node status, HER2 expression, tumors TIMP-1 and MMP-13 were independent prognostic factors.


CONCLUSIONS
MMP-13 protein expressed by tumor cells correlates with the invasion and metastasis of breast carcinoma, and therefore, may serve as a poor prognostic marker for the patient.
Zhang
Bin
B
Department of Breast Neoplasms, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China.
Liu
Yan-Xue
YX
Cao
Wen-Feng
WF
Cao
Xu-Chen
XC
Ning
Lian-Sheng
LS
Hao
Xi-Shan
XS
D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D053509:Matrix Metalloproteinase 13 / Q000032:analysis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009361:Neoplasm Invasiveness / Q000175:diagnosis* / Q000503:physiopathology; D009367:Neoplasm Staging / Q000145:classification; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone / Q000032:analysis
D014408:Biomarkers, Tumor; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone