c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression and prognostic implications
| Autor: | K Bousboukea, Fanie Gigelou, M Scliri, P Korkolopoulou, E. Patsouris, I Thymara, Georgia Levidou, Nicolaos V. Michalopoulos, Andreas C. Lazaris, Michalis Tzivras, Angelica A. Saetta, Anastasia E. Konstantinidou, N. Apostolikas |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Fas Ligand Protein Histology Colorectal cancer CASP8 and FADD-Like Apoptosis Regulating Protein Apoptosis Fas ligand Pathology and Forensic Medicine Immune system medicine Humans fas Receptor Aged Retrospective Studies Aged 80 and over business.industry Hazard ratio Anatomical pathology General Medicine Middle Aged Prognosis medicine.disease Immunohistochemistry Flip Cancer research Female Colorectal Neoplasms business |
| Zdroj: | Histopathology. 51:150-156 |
| ISSN: | 1365-2559 0309-0167 |
| DOI: | 10.1111/j.1365-2559.2007.02723.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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