Prognostic significance of fascin overexpression in human esophageal squamous cell carcinoma

Yosuke Hashimoto, Tetsuo Ito, Harutaka Inoue, Tomoyuki Okumura, Eiji Tanaka, Shigeru Tsunoda, Motoshige Higashiyama, Go Watanabe, Masayuki Imamura, Yutaka Shimada
Clinical Cancer Research 2005 April 1, 11 (7): 2597-605

PURPOSE: Fascin, an actin bundling protein, induces membrane protrusions and increased cell motility in various transformed cells. The expression of fascin in epithelial neoplasms has been described only recently, and the role of fascin in esophageal squamous cell carcinoma (ESCC) is still unknown.

EXPERIMENTAL DESIGN: Paraffin sections of 200 patients with ESCC were immunohistochemically investigated. The expression levels of fascin mRNA in 20 ESCC tissues were compared with that in corresponding normal esophageal epithelium by semiquantitative reverse transcription-PCR. We also examined fascin protein expression in 33 ESCC cell lines. The role of fascin in cell motility and invasiveness in ESCC cells was assessed by the vector-based small interfering RNA.

RESULTS: In immunohistochemical study, the intensity of fascin expression was usually increased in the tumor compared with that in normal epithelium. Fascin overexpression was significantly associated with a poor prognosis (immunoreactive rate, P = 0.033; immunoreactive intensity, P = 0.031). The fascin immunoreactive rate was associated with extent of the tumor (P = 0.002) and lymph node metastasis (P = 0.003). Multivariate analysis showed that fascin expression intensity was an independent prognostic factor, but the immunoreactive rate was not. In addition, up-regulation of fascin mRNA was found in 60% (12 of 20) of patients. In vitro study revealed that all 33 ESCC cell lines expressed fascin protein at a certain level. KYSE170, one of the fascin-overexpressed cells, decreased its motile and invasive properties after down-regulation of fascin expression.

CONCLUSION: Our findings suggest that fascin overexpression may play an important role in the progression of ESCC.

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