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The molecular role of Fra-1 and its prognostic significance in human esophageal squamous cell carcinoma
Article first published online: 25 OCT 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 13, pages 3387–3396, 1 July 2012
How to Cite
Usui, A., Hoshino, I., Akutsu, Y., Sakata, H., Nishimori, T., Murakami, K., Kano, M., Shuto, K. and Matsubara, H. (2012), The molecular role of Fra-1 and its prognostic significance in human esophageal squamous cell carcinoma. Cancer, 118: 3387–3396. doi: 10.1002/cncr.26652
- Issue published online: 18 JUN 2012
- Article first published online: 25 OCT 2011
- Manuscript Accepted: 7 SEP 2011
- Manuscript Revised: 22 AUG 2011
- Manuscript Received: 14 MAY 2011
- esophageal squamous cell carcinoma;
- cell proliferation;
- cell migration;
- cell invasion;
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.
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.
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.
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. © 2011 American Cancer Society.