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Journal of Cancer Research and Clinical Oncology

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01.03.2015 | Original Article – Clinical Oncology

The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis

verfasst von: Gustav J. Ullenhag, Ahmad Al-Attar, Abhik Mukherjee, Andrew R. Green, Ian O. Ellis, Lindy G. Durrant

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2015

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Abstract

Background

Breast cancer is the most common cancer in women. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway transmits apoptotic signals. Novel anticancer agents that activate this system are in clinical development, including anti-breast cancer.

Methods

The tissue microarray technique was applied. We used an array of breast cancer tissues from a large group of patients (>800) to assess the protein expression of TRAIL-R1, TRAIL-R2, the long isoform of FLICE-inhibitory protein and total FLICE-inhibitory protein (FLIP_L and FLIP_T). Disease-free survival was examined by Kaplan–Meier estimates and the log-rank test. The independence of prognostic factors was determined by Cox multivariate analysis.

Results

High intra-tumoral expression of all these proteins of the TRAIL pathway was found. The TRAIL receptors and FLIP_L were not associated with survival. On univariate analysis, strong FLIP_T expression was associated with a significantly better survival (p = 0.001). On multivariate analysis using the Cox proportional hazards model, FLIP_T phenotype was significantly associated with a good prognosis in this series (HR 0.52, 95 % CI 0.35–0.78, p = 0.039). Results indicate that this association is valid for all the biological subtypes of breast cancer. The expression of FLIP_T was especially high in the luminal subtype, known for its good prognosis.

Conclusions

These findings support the use of agonistic TRAIL antibodies and drugs targeting FLIP in breast cancer patients. Over-expression of FLIP_T but not TRAIL-R1, TRAIL-R2 or FLIP_L provides stage-independent prognostic information in breast cancer patients. This indicates a clinically less aggressive phenotype.

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Titel: The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis
verfasst von: Gustav J. Ullenhag
Ahmad Al-Attar
Abhik Mukherjee
Andrew R. Green
Ian O. Ellis
Lindy G. Durrant
Publikationsdatum: 01.03.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-014-1822-0

Springer Medizin

The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis