Linked Life Data

19680616

Source:http://linkedlifedata.com/resource/pubmed/id/19680616

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-10-6
pubmed:abstractText
TNF-related apoptosis-inducing ligand (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 no or only a truncated cytoplasmic death domain. Consequently, they cannot induce apoptosis and instead have been proposed to inhibit apoptosis induction by TRAIL. Agonists for the apoptosis-inducing TRAIL-R1 and TRAIL-R2 are currently tested in clinical trials. To determine the expression pattern of all surface-bound TRAIL receptors and their prognostic clinical value, we investigated tumour samples of 311 patients with breast cancer by immunohistochemistry. TRAIL receptor expression profiles were correlated with clinico-pathological data, disease-free survival and overall survival. TRAIL-R1 was more strongly expressed in better differentiated tumours, and correlated positively with surrogate markers of a better prognosis (hormone receptor status, Bcl-2, negative nodal status), but negatively with the expression of Her2/neu and the proliferation marker Ki67. In contrast, TRAIL-R2 and TRAIL-R4 expression correlated with higher tumour grades, higher Ki67 index, higher Her2/neu expression and a positive nodal status at the time of diagnosis, but with lower expression of Bcl-2. Thus, the TRAIL receptor expression pattern was predictive of nodal status. Patients with grade 1 and 2 tumours, who had TRAIL-R2 but no TRAIL-R1, showed a positive lymph node status in 47% of the cases. Vice versa, only 19% had a positive nodal status with high TRAIL-R1 but low TRAIL-R2. Most strikingly, TRAIL-R4 and -R2 expression negatively correlated with overall survival of breast cancer patients. Although TRAIL-R2 correlated with more aggressive tumour behaviour, mammary carcinoma could be sensitised to TRAIL-R2-induced apoptosis, suggesting that TRAIL-R2 might therefore be used to therapeutically target such tumours. Hence, determination of the TRAIL receptor expression profile may aid in defining which breast cancer patients have a higher risk of lymph node metastasis and worse overall survival and on the other hand will help to guide TRAIL-based tumour therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1432-1440
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
87
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
995-1007
pubmed:dateRevised
2011-7-8
pubmed:meshHeading
pubmed-meshheading:19680616-Adult, pubmed-meshheading:19680616-Aged, pubmed-meshheading:19680616-Aged, 80 and over, pubmed-meshheading:19680616-Animals, pubmed-meshheading:19680616-Antibiotics, Antineoplastic, pubmed-meshheading:19680616-Apoptosis, pubmed-meshheading:19680616-Breast Neoplasms, pubmed-meshheading:19680616-Cell Line, Tumor, pubmed-meshheading:19680616-Disease-Free Survival, pubmed-meshheading:19680616-Doxorubicin, pubmed-meshheading:19680616-Female, pubmed-meshheading:19680616-Humans, pubmed-meshheading:19680616-Immunohistochemistry, pubmed-meshheading:19680616-Kaplan-Meier Estimate, pubmed-meshheading:19680616-Middle Aged, pubmed-meshheading:19680616-Prognosis, pubmed-meshheading:19680616-Protein Isoforms, pubmed-meshheading:19680616-Receptors, TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:19680616-Reproducibility of Results, pubmed-meshheading:19680616-Tissue Array Analysis, pubmed-meshheading:19680616-Tumor Markers, Biological
pubmed:year
2009
pubmed:articleTitle
Prognostic significance of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor expression in patients with breast cancer.
pubmed:affiliation
Division of Apoptosis Regulation (D040), German Cancer Research Center (DKFZ), Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't