Fibronectin expression in carcinoma cells correlates with tumor aggressiveness and poor clinical outcome in patients with invasive breast cancer

Abstract

Fibronectin (FN), a large heterodimeric glycoprotein, can be found in soluble form in plasma or in insoluble form as an extracellular matrix protein. Cellular FN is produced by various types of benign and malignant epithelial and mesenchymal cells and is widely distributed in malignant tumors. We evaluated FN expression in cancer cells (epithelial FN; E-FN) and intratumor stroma (stromal FN, S-FN) of 1596 invasive breast cancer samples using immunohistochemistry on tissue microarrays. Correlations of FN expression with clinicopathologic factors and patient survival were investigated. Among 1512 informative cases, E-FN expression was observed in 355 (23.5%) cases, and S-FN expression showed no/weak staining in 362 (23.9%), moderate staining in 744 (49.2%), and strong staining in 406 (26.9%) cases. E-FN expression was correlated with advanced pT (P < .001) and pN (P < .001), histologic type (P = .006), high histologic grade (P < .001), lymphovascular invasion (P < .001), hormone receptor negativity (P < .001), and human epidermal growth factor receptor-2 (HER2) positivity (P < .001). Strong S-FN expression showed an association with advanced pN (P = .002), histologic type (P < .001), high histologic grade (P < .001), lymphovascular invasion (P < .001), and HER2 positivity (P < .001). Patients with E-FN expression showed worse overall survival (P < .001) and disease-free survival (P < .001) than did those with negative expression of FN. E-FN expression was an independent prognostic factor, especially in the hormone receptor-positive group. Expression of S-FN did not have a significant effect on patient survival. In conclusion, E-FN expression could be a promising prognostic marker in patients with invasive breast cancer.

Keywords: Breast neoplasms; Fibronectin; Immunohistochemistry; Prognosis.