Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Receptor Expression in Patients with Neuroendocrine Neoplasia

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Introduction: Targeting the death receptor pathway of apoptosis represents a promising approach for the development of novel cancer therapeutics. TNF-related TRAIL induces apoptosis upon binding to TRAIL receptors 1 and 2 (TRAIL-R1/DR4 and TRAIL-R2/DR5). TRAIL-R3 (DcR1) and TRAIL-R4 (DcR2) have been reported to block TRAIL-mediated apoptosis upon overexpression. Specially agonists for the apoptosis-inducing TRAIL-R1 and TRAIL-R2 are currently tested in clinical trials.

Aim(s): As studies on TRAIL receptors in neuroendocrine neoplasia (NEN) are currently unavailable, we embarked to investigate the role of TRAIL receptors exprssion in a cohort of patients with NEN.

Materials and methods: 958 tissue samples of human neuroendocrine tumors of the gastrointestinal tract, its metastases and also healthy tissue of 144 NET patients were immunohistochemically stained and the expression levels of TRAIL-R1, TRAIL-R2, TRAIL-R3, TRAIL-R4, Caspase-8, cFLIP and PARP were quantified using an automatic software-based algorithm. In a next step we gathered the clinical data of our 144 patients and compared the expression levels of the aforementioned proteins depending on tissue grading, tissue origin, UICC staging and survival in an 8-year period.

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author:

Authors: Sättele R, Jann H, Fischer C, Pape U, Schefold J,

Keywords: TRAIL, apoptosis, NENs,