TY - JOUR
TI - c-FLIP expression in colorectal carcinomas: association with Fas/FasL
expression and prognostic implications
AU - Korkolopoulou, P.
AU - Saetta, A. A.
AU - Levidou, G.
AU - Gigelou, F. and
AU - Lazaris, A.
AU - Thymara, I.
AU - Scliri, M.
AU - Bousboukea, K. and
AU - Michalopoulos, N. V.
AU - Apostolikas, N.
AU - Konstantinidou, A. and
AU - Tzivras, M.
AU - Patsouris, E.
JO - Diagnostic Histopathology
PY - 2007
VL - 51
TODO - 2
SP - 150-156
PB - Blackwell Publishing Inc.
SN - 1756-2317
TODO - 10.1111/j.1365-2559.2007.02723.x
TODO - c-FLIP; colorectal carcinoma; Fas; FasL; immunohistochemistry
TODO - 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.
ER -