@article{3117632,
    title = "c-FLIP expression in colorectal carcinomas: association with Fas/FasL
expression and prognostic implications",
    author = "Korkolopoulou, P. and Saetta, A. A. and Levidou, G. and Gigelou, F. and and Lazaris, A. and Thymara, I. and Scliri, M. and Bousboukea, K. and and Michalopoulos, N. V. and Apostolikas, N. and Konstantinidou, A. and and Tzivras, M. and Patsouris, E.",
    journal = "Diagnostic Histopathology",
    year = "2007",
    volume = "51",
    number = "2",
    pages = "150-156",
    publisher = "Blackwell Publishing Inc.",
    issn = "1756-2317",
    doi = "10.1111/j.1365-2559.2007.02723.x",
    keywords = "c-FLIP; colorectal carcinoma; Fas; FasL; immunohistochemistry",
    abstract = "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."
}