Expression profiles of TRAIL and its receptors in normal, hyperplastic, and malignant endometrial tissues: Hints on endometrial cancer biology

INTRODUCTION: Endometrial cancer is the sixth most common neoplasm in women worldwide, with a rising incidence largely attributed to the ongoing obesity epidemic. TNF-Related Apoptosis-Inducing Ligand (TRAIL) and TRAIL receptors have been tested for their predictive, diagnostic, and prognostic values in various cancers, as well as for possible use in combination therapies. The roles of TRAIL and its receptors in endometrial tissue biology has not yet been cleared, and the potential of these molecules as biomarkers in endometrial cancer is yet to be defined. We investigated the expression profiles of TRAIL and its transmembrane receptors during endometrial carcinogenesis to evaluate their potential as prognostic markers.
METHODS: Paraffin-embedded normal endometrium (n=18), endometrial hyperplasia (n=27), and endometrioid endometrial adenocarcinoma tissues (n=100) were analysed for TRAIL and receptor expression profiles via immunohistochemical staining. Apoptotic indexes in the corresponding tissues were defined by TUNEL assay.
RESULTS: Endometrial carcinoma displayed decreased TRAIL and DR4 expressions compared to the normal endometrium, while increased DR5 and decoy receptor (DcR1 and DcR2) expressions were evident. The complex atypical hyperplasia displayed the most similar expression profiles to the endometrial carcinoma, in accordance with the greatest risk of progression to endometrial carcinoma attributed to this tissue type. TRAIL/TRAIL receptor expression levels did not correlate with the prognostic factors of tumor stage or grade, or depth of myometrial invasion.
DISCUSSION AND CONCLUSION: Overall, distinct profiles of TRAIL and its receptor expressions were evident in progression from normal endometrium to hyperplasia and cancer, which may indicate significance of TRAIL signaling in the course of endometrial carcinoma development.