Prognostic significance of fascin overexpression in human esophageal squamous cell carcinoma
Prognostic significance of fascin overexpression in human esophageal squamous cell carcinoma
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DOI：
10.1158/1078-0432.ccr-04-1378
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发表时间：
2005-04-01
影响因子：
11.5
通讯作者：
Shimada, Y
中科院分区：
文献类型：
--
作者：
Hashimoto, Y;Ito, T;Shimada, Y
目的：肌动蛋白集束蛋白 Fascin在多种转化细胞中诱导膜突出并增加细胞运动性。Fascin在上皮肿瘤中的表达直到近期才被描述，其在食管鳞状细胞癌（ESCC）中的作用仍不清楚。
实验设计：对200例ESCC患者的石蜡切片进行免疫组化研究。通过半定量逆转录 - PCR比较20例ESCC组织中Fascin mRNA的表达水平与相应正常食管上皮中的表达水平。我们还检测了33种ESCC细胞系中Fascin蛋白的表达。通过基于载体的小干扰RNA评估Fascin在ESCC细胞运动性和侵袭性中的作用。
结果：在免疫组化研究中，与正常上皮相比，肿瘤中Fascin的表达强度通常增加。Fascin过表达与不良预后显著相关（免疫反应率，P = 0.033；免疫反应强度，P = 0.031）。Fascin免疫反应率与肿瘤范围（P = 0.002）和淋巴结转移（P = 0.003）相关。多变量分析显示Fascin表达强度是一个独立的预后因素，但免疫反应率不是。此外，在60%（20例中的12例）的患者中发现Fascin mRNA上调。体外研究显示所有33种ESCC细胞系在一定水平上表达Fascin蛋白。KYSE170是Fascin过表达的细胞之一，在Fascin表达下调后其运动和侵袭特性降低。
结论：我们的研究结果表明Fascin过表达可能在ESCC的进展中起重要作用。
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 m RNA 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.