Περίληψη:
Objectives. To investigate the incidence of Fas (exon 9) mutations and
the expression of Fas, Fas-Fas ligand (FasL) system, and cellular
FLICE-like inhibitory protein (c-FLIP) in relation to standard
clinicopathologic parameters and patient outcome in bladder carcinoma.
Disruption of apoptotic cell death has been implicated in tumor
aggressiveness in bladder urothelial carcinomas. The FasL system is
involved in the execution of apoptosis induced by the immune system.
c-FLIP protein constitutes an important endogenous inhibitor of Fas and
other death receptor-mediated apoptosis.
Methods. The expression of Fas, FasL, and c-FLIP was quantified
immunohistochemically in paraffin-embedded tissues from 53 patients for
whom clinical information was available. DNA extracted from the same
samples was screened for mutations in Fas exon 9 by single-strand
conformation polymorphism and sequencing. The effect of Fas, FasL, and
c-FLIP on clinical outcome was assessed by univariate and multivariate
analyses.
Results. Positive immunostaining was detected for Fas, FasL, and c-FLIP
in 72%, 66%, and 81% of cases, respectively. Concurrent expression of
Fas and FasL was seen in 27 samples (51%), of which 22 (81.5%) also
displayed c-FLIP positivity. FasL and c-FLIP expression increased with
advancing stage but was absent from normal urothelium. None of the 53
urothelial carcinoma samples analyzed showed evidence of mutations by
polymerase chain reaction single-strand conformation polymorphism and
direct sequencing. Survival analysis demonstrated that although both
FasL and c-FLIP expression adversely affected survival, only c-FLIP
remained statistically significant on multivariate analysis.
Conclusions. The frequent expression and coexpression of Fas, FasL, and
c-FLIP in urothelial carcinomas implicates c-FLIP as an inhibitor of the
Fas-FasL-induced death pathway in these tumors. Moreover, c-FLIP conveys
independent prognostic information in the presence of classical
prognosticators. (C) 2004 Elsevier Inc.
Συγγραφείς:
Korkolopoulou, P
Goudopoulou, A
Voutsinas, G
Thomas-Tsagli,
E
Kapralos, P
Patsouris, E
Saetta, AA
