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DcR1 expression in endometrial carcinomas.

Jordi Tarragona1, Nuria Llecha, Maria Santacana

  • 1Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida IRBLLEIDA, Av Alcalde Rovira Roure 80, 25198 Lleida, Spain. tarragona@gss.scs.e

Virchows Archiv : an International Journal of Pathology
|November 26, 2009
PubMed
Summary

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Decoy receptor 1 (DcR1) is frequently expressed in endometrial carcinoma (EC), potentially causing resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy. This study assessed DcR1 expression in EC tissues.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Research

Background:

  • The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway is crucial for extrinsic apoptosis.
  • Decoy receptors, such as DcR1, can inhibit TRAIL-mediated apoptosis by binding TRAIL, preventing it from activating functional death receptors.
  • Understanding DcR1 expression in endometrial carcinoma (EC) is vital for developing targeted therapies.

Purpose of the Study:

  • To investigate the expression levels of DcR1 in normal endometrial (NE) tissue and endometrial carcinoma (EC).
  • To determine if DcR1 expression correlates with clinical parameters like stage, histological type, and grade in EC.
  • To assess the potential role of DcR1 in TRAIL-induced apoptosis resistance in EC.

Main Methods:

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  • Immunohistochemistry (IHC) was used to assess DcR1 protein expression in tissue microarrays of 80 NE and 62 EC samples.
  • Quantitative real-time PCR (RT-PCR) was employed to measure DcR1 mRNA expression in 19 NE and 28 EC samples.
  • Results were statistically correlated with EC stage, histological type, and grade.

    • Main Results:

    • Cytoplasmic DcR1 expression was observed in 79.6% of NE and 98.1% of EC samples by IHC.
    • While DcR1 was frequently detected in EC, no significant association was found with histological type, grade, or stage.
    • Quantitative RT-PCR revealed increased DcR1 mRNA expression (≥5-fold basal levels) in 46.4% of EC cases, with elevated levels across various stages.

    Conclusions:

    • DcR1 is commonly expressed in endometrial carcinoma.
    • Increased DcR1 expression in a subset of EC may contribute to resistance to TRAIL-induced apoptosis.
    • Targeting DcR1 could be a potential therapeutic strategy for overcoming TRAIL resistance in endometrial cancer.