c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression and prognostic implications
c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression and prognostic implications
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DOI：
10.1111/j.1365-2559.2007.02723.x
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发表时间：
2007-08-01
期刊：
影响因子：
6.4
通讯作者：
Patsouris, E.
中科院分区：
文献类型：
--
作者：
Korkolopoulou, P.;Saetta, A. A.;Patsouris, E.
目的：凋亡细胞死亡的破坏与结肠癌发生中的肿瘤侵袭性有关。Fas-Fas配体（FasL）系统参与免疫系统诱导的细胞凋亡的执行。c-FLIP蛋白构成了Fas和其他（TRAIL）死亡受体介导的细胞凋亡的抑制剂。本研究的目的是探讨Fas，FasL和c-FLIP的同时表达与标准的临床病理参数和患者的结直肠cancer.Methods和结果的关系：Fas，FasL和c-FLIP蛋白表达水平进行定量化学石蜡包埋组织从90例。Fas、Fast和c-FLIP的免疫阳性率分别为71%、35.5%和68.8%。28例（31%）标本同时表达Fas/FasL，其中24例（85.7%）c-FLIP阳性（P = 0.04）。c-FLIP过表达（> 10%）倾向于在较高阶段肿瘤中略微占优势（P = 0.09）。此外，FasL和c-FLIP对生存率有不利影响，（分别为P = 0.001和P = 0.0024）和多变量分析[风险比（HR）3.491，P = 0.005和HR 2.960，P = 0.036]。Fas、FasL和c-FLIP在结直肠癌中的频繁表达和共表达暗示c-FLIP是这些肿瘤中Fas-FasL诱导的死亡途径的抑制剂。此外，c-FLIP传达独立的预后信息，在经典的预测。
Aims: Disruption of apoptotic cell death has been implicated in tumour aggressiveness in colonic carcinogenesis. The Fas-Fas ligand (FasL) system is involved in the execution of apoptosis induced by the immune system. c-FLIP protein constitutes an inhibitor of Fas and other (TRAIL) death receptor-mediated apoptosis. The aim of this study was to investigate the simultaneous expression of Fas, FasL and c-FLIP in relation to standard clinicopathological parameters and patients' outcome in colorectal cancer.Methods and results: Levels of Fas, FasL and c-FLIP protein expression were quantified immunohistochemically in paraffin-embedded tissues from 90 patients. Immunopositivity was detected for Fas, Fast, and c-FLIP in 71%, 35.5% and 68.8% of cases, respectively. Concurrent expression of Fas/FasL was seen in 28 samples (31%), of which 24 (85.7%) also displayed c-FLIP positivity (P = 0.04). c-FLIP overexpression (> 10%) tended to prevail marginally in higher stage tumours (P = 0.09). Additionally, FasL and c-FLIP adversely affected survival on both univariate (P = 0.001 and P = 0.0024, respectively) and multivariate analysis [hazard ratio (HR) 3.491, P = 0.005 and HR 2.960, P = 0.036, respectively].Conclusions: The frequent expression and coexpression of Fas, FasL and c-FLIP in colorectal carcinoma implicates c-FLIP as an inhibitor of the Fas-FasL-induced death pathway in these tumours. Moreover, c-FLIP conveys independent prognostic information in the presence of classical prognosticators.