Breast Cancers Secreting Sialyl-Fibronectin in the Blood are Less Likely to Cause Epithelial-mesenchymal Transition and Have a Good Prognosis

Abstract

Abstract Purpose: Elevated blood fibronectin (FN) levels have been observed in various cancers; however, their significance is controversial. We measured sialyl-fibronectin (S-FN), a type of FN secreted by tumor cells in the blood, and investigated whether blood S-FN secretion is associated with cancer malignancy and recurrent metastasis. Methods: We constructed an enzyme-linked immunosorbent assay (ELISA) system that recognized S-FN as an antigen and measured the amount of S-FN secreted into the blood of 89 breast tumor patients. The relationship between S-FN secretion and prognostic predictors was statistically examined. Immunostaining was performed to identify the site of S-FN secretion in the breast tissue. Results: Among the 82 breast cancer cases, 21 (25.6%, 21/82) and 61 (74.4%, 61/82) were blood S-FN-positive and S-FN-negative, respectively. Regarding prognostic predictors in blood S-FN-positive and S-FN-negative cases, a significant difference was found in three factors of locoregional recurrence (p = 0.026), remote metastasis (p = 0.049), and histological margin (p = 0.001). Locoregional recurrence was associated with positive histological margins in S-FN-positive cases. However, remote metastasis was associated with N-factor and histological classification (HC) in S-FN-negative cases. Furthermore, S-FN particles were detected in the cytoplasm of breast cancer cells through immunostaining. After the onset of recurrent metastasis, two S-FN-positive and six S-FN-negative patients received anticancer drug treatment; however, further progression was observed in five S-FN-negative patients. Conclusion S-FN-positive cases are less likely to cause distant metastases, have a better prognosis, and may be less resistant to therapeutic agents than S-FN-negative cases, which contain many epithelial-mesenchymal transition cells. Trial registration number and Date: The study was approved by the Ethics Committee of Jikei Medical University, Tokyo, Japan, in 2011 [No. 27-112 (7997)].