Sialic Acid-Fibronectin-negative and Vimentin-positive Breast Cancers Have Poor Prognoses due to Epithelial-Mesenchymal Transition

Background/Aim: Elevated fibronectin levels have been observed in various cancers; however, whether they are related to the actual malignancy remains controversial. We herein measured blood levels of sialic acid-fibronectin (S-FN), a type of autocrine cellular fibronectin secreted by breast cancer cells and investigate whether S-FN secretion is associated with the malignancy through epithelial-mesenchymal transition (EMT), as well as recurrent metastasis.

Patients and Methods: Blood S-FN was detected in samples from 82 patients with breast carcinoma using ELISA. Vimentin immunostaining was performed in recurrent metastases cases to identify mesenchymal state cancer cells (MCCs) induced by EMT.

Results: Of the 82 patients, twenty- one patients (25.6%) were positive for S-FN. Twelve patients (14.6%) had recurrent metastases, including five with local recurrence (LR) and seven with remote metastasis (RM). Vimentin-positive cancer cells (VPCCs), suggesting the presence of MCCs in the tumor, had 1-10 (1+) in three S-FN-positive patients of LR. However, their histological margins showed remnants of cancer cells. Conversely, two S-FN-negative patients had VPCCs between 11-50 (2+) and did not have residual cancer at the margins, but experienced LR. Of the seven patients with RM, one S-FN-positive patient was VPCCs (1+) and had stable disease (SD). The other six S-FN-negative patients had VPCCs (1+) in two patients, and ≥ (2+) in four patients. One patient with VPCCs (1+) had SD, but four patients with VPCCs ≥ (2+) were treatment-resistant and had progressive disease (PD).

Conclusion: S-FN-negative patients showed treatment resistance and poor prognosis due to the high presence of EMT-induced MCCs in breast cancer.