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.
Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Akihiro
A
Usui
Isamu
I
Hoshino
Yasunori
Y
Akutsu
Haruhito
H
Sakata
Takanori
T
Nishimori
Kentaro
K
Murakami
Masayuki
M
Kano
Kiyohiko
K
Shuto
Hisahiro
H
Matsubara
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016019:Survival Analysis; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D000099169:Fos-Related Antigen 1