Expression and prognostic significance of fibronectin and matrix metalloproteases in breast cancer metastasis

• Published in: Histopathology Vol. 64; no. 4; pp. 512 - 522
• Main Authors: Fernandez-Garcia, Belen, Eiró, Noemí, Marín, Laura, González-Reyes, Salomé, González, Luis O, Lamelas, Maria Luz, Vizoso, Francisco J
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-03-2014; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Biomarkers, Tumor - metabolism; Breast cancer; breast carcinoma; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - pathology; Carcinoma, Ductal, Breast - secondary; Female; fibronectin; Fibronectins - metabolism; Humans; Immunohistochemistry; Matrix Metalloproteinase 11 - metabolism; Matrix Metalloproteinase 7 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinases - metabolism; Medical research; metastasis; Middle Aged; MMPs; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Prognosis; Tissue Array Analysis; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tissue Inhibitor of Metalloproteinase-2 - metabolism; Tissue Inhibitor of Metalloproteinases - metabolism; Tumors; fibronectin; breast carcinoma; metastasis; prognosis; MMPs
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.12300

Aims
Fibronectin (FN) has attracted interest in cancer research, owing to its role in tumour progression. The aims of this study were to investigate the expression and clinical relevance of FN in breast cancer, and to explore its relationship with the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs).
Methods and results
An immunohistochemical study was performed using tumours from 110 breast cancer patients, with tissue arrays and specific antibodies against FN, MMP‐7, MMP‐9, MMP‐11, TIMP‐1, and TIMP‐2. The results indicated that FN expression was related to tumour size, histological grade, and MMP‐9 expression. Tumours with high FN expression by tumour cells were significantly associated with a higher probability of metastasis, poorer overall survival, and expression of MMP‐7, MMP‐9, MMP‐11, TIMP‐1 and TIMP‐2 by mononuclear inflammatory cells (MICs). In addition, the combination of FN expression by tumour cells and MMP‐11 by MICs was strongly associated with distant metastasis development.
Conclusions
Breast carcinomas with distant metastasis frequently have tumour cells expressing intracellular FN. There is a strong association between FN expression by tumour cells and MMP or TIMP expression by stromal MICs, and this may represent crosstalk that is of prognostic relevance in breast cancer.