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Updated: Jul 14, 2026
Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression and prognostic implications
P Korkolopoulou1, A A Saetta, G Levidou
1Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
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, FasL 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.
Insights
In colorectal cancer, the study found that Fas Ligand (FasL) and c-FLIP protein expression negatively impact patient survival. c-FLIP also appears to inhibit the Fas-FasL-induced apoptosis pathway in these tumors.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Disruption of apoptotic cell death contributes to tumor aggressiveness in colorectal cancer.
- The Fas-Fas ligand (FasL) system mediates immune-induced apoptosis.
- c-FLIP protein inhibits Fas and TRAIL death receptor-mediated apoptosis.
Purpose of the Study:
- Investigate the expression of Fas, FasL, and c-FLIP in colorectal cancer.
- Correlate expression with clinicopathological parameters and patient outcomes.
- Determine the role of c-FLIP in the Fas-FasL apoptotic pathway.
Main Methods:
- Immunohistochemical analysis of Fas, FasL, and c-FLIP in 90 colorectal cancer tissues.
- Quantification of protein expression levels.
- Univariate and multivariate survival analyses.
Main Results:
- Fas, FasL, and c-FLIP were expressed in 71%, 35.5%, and 68.8% of cases, respectively.
- Concurrent Fas/FasL expression was observed in 31% of samples, with 85.7% also showing c-FLIP positivity.
- FasL and c-FLIP expression were independently associated with adverse patient survival (P < 0.05).
Conclusions:
- Frequent coexpression of Fas, FasL, and c-FLIP suggests c-FLIP inhibits Fas-FasL-induced apoptosis in colorectal carcinoma.
- c-FLIP provides independent prognostic information beyond established prognostic factors.
