The molecular role of Fra-1 and its prognostic significance in human esophageal squamous cell carcinoma

BACKGROUND: The expression of Fra-1 (Fos related antigen 1) involves tumor progression and invasion, and its gene ablation could suppress the invasive phenotypes of human tumor cells. The authors investigated the significance of Fra-1 expression in esophageal squamous cell carcinoma (ESCC) and studied the effect of its down-regulation on cell proliferation, motility, and invasion. METHODS: Surgical specimens from 164 patients with ESCC were evaluated. Fra-1 expression in the primary tumor along with metastatic lymph nodes was compared among various clinicopathological characteristics, and overall survival was analyzed. The rate and intensity of Fra-1 immunoreactivity were also investigated. The molecular role of Fra-1 was assessed by its down-regulation in human ESCC cell lines. RESULTS: Fra-1 expression was positive in 127 (77.4%) ESCC patients. Immunoreactivity was localized to the marginal areas of the ESCC tumors. Positive Fra-1 expression correlated with depth of tumor, lymph node metastasis, stage, and infiltrative growth pattern. A significant difference was seen in the survival between tumors with and without Fra-1, and positive Fra-1 expression was revealed to be an independent factor related to poor prognosis. Patients with metastatic lymph nodes with positive Fra-1 expression presented decreased survival compared with negative Fra-1 expression. After the down-regulation of Fra-1 expression, a significant decrease in cell proliferation, motility, and invasion was observed. CONCLUSIONS: This study demonstrated ESCC patients positive for Fra-1 to be associated with poor prognosis. The findings also suggest that Fra-1 regulation may play an important role in the progression of ESCC. Cancer 2011. (c) 2011 American Cancer Society.