DcR1 expression in endometrial carcinomas

Abstract

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which mediates apoptosis by the extrinsic pathway. Up-regulation of decoy receptors, DcR1 and DcR2, may result in diminished binding of TRAIL to their functional receptors. DcR1 expression was assessed in normal endometrial tissue (NE) and endometrial carcinoma (EC) samples by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (PCR). IHC was performed in two tissue microarrays; one composed of 80 samples of NE and a second one constructed from paraffin-embedded blocks of 62 EC. For quantitative real-time RT-PCR analysis, RNA was obtained from 19 NE and 28 EC samples using Trizol. mRNA expression of DcR1 was assessed with Taqman-based assays in an Abi-Prism 700 SDS. Results were correlated with stage, histological type, and grade. By IHC, cytoplasmic expression of DcR1 was frequently seen in NE (79.6%) and varied according to the menstrual cycle. Positive DcR1 immunostaining was also detected in EC (98.1% of the cases) without any specific statistical association with histological type, grade, and stage. By quantitative real-time PCR, all NE had similar levels of DcR1expression (0.8-1.7 RQ), which were considered the basal levels of DcR1 expression in NE. Increased DcR1 expression (> or =5-fold higher than the basal levels) was detected in 13 of 28 EC (46.4%). High DcR1 expression levels were found in ECs of different stages: IA, four of 12 (33%); IB, two of four (50%); IC, four of six (66%); and IIA and IIB three of six (50%). Results suggest that DcR1 expression occurs in a subset of EC and may contribute to resistance to TRAIL-induced apoptosis.

Membrane expression of TRAIL receptors DR4, DR5, DcR1 and DcR2 in the normal endometrium, atypical endometrial hyperplasia and endometrioid adenocarcinoma: a tissue microarray study

“…Similarly, the cytoplasmic expression of DcR1 and DcR2 was reported, e.g., in primary and metastatic brain tumors [8] and in prostate cancer [27]. In endometrial cancer, DcR1 cytoplasmic expression was evaluated by Tarragona et al [15]. The authors studied 62 cases of endometrial cancers by tissue microarray, and found DcR1 to be present in 98.1 % of cases [15].…”

“…In contrast to this, Koornstra et al [9] describe a lack of correlation of DR4 and DR5 cytoplasmic expression with grading and staging in cancer of the colon, and Zhuang et al [28] found DcR1 and DcR2 cytoplasmic expression not to be related to progression of neoplasmic disease. In endometrial cancer patients, Tarragona et al [15] did not confirm the association of DcR1 expression with histological type of the cancer (EAC vs. non-EAC), its grade and stage, as well.…”

“…In endometrial cancer, DcR1 cytoplasmic expression was evaluated by Tarragona et al [15]. The authors studied 62 cases of endometrial cancers by tissue microarray, and found DcR1 to be present in 98.1 % of cases [15]. …”

“…Although endometrial cancer is the most common gynecologic malignancy, to date there have been only a few studies attempting to evaluate the expression of TRAIL receptors [14, 15]. …”

Therapeutic targeting of the TNF superfamily: A promising treatment for advanced endometrial adenocarcinoma

“…In EAC, this may be at least in part due to the over expression of the decoy receptor DcR1. It has been demonstrated that DcR1 is over expressed in EAC and it competitively inhibits the attachment of the TRAIL ligand to the DD receptors [55]. An interesting study by Dolcet et al demonstrated that TRAIL fails to trigger apoptosis in endometrial cancer cells, indicating resistance probably mediated by the FLICE-inhibitory protein (FLIP) [56].…”