The expression of death receptor systems TRAIL-R1/-R2/-R4, CD95 and TNF-R1 and their cognate ligands in pancreatic ductal adenocarcinoma
2019
The expression of five members of the TNF
receptor superfamily and two of their ligands in human
pancreatic ductal adenocarcinoma were investigated by
immunohistochemistry. 41 patients with histologically
confirmed ductal carcinoma of the pancreas were
enrolled in this study in order (i) to compare the
individual TNFR-SF expression and their ligands in
PDAC-cells and (ii) to investigate their correlation with
survival data. All patients had undergone
pancreaticoduodenectomy and were staged as
pT3N1M0. Immunostaining was done on FFPE tissue
sections of the tumor tissue, using antibodies directed
against TRAIL-Receptor-1, -2 and -4, TRAIL, CD95,
TNF-Receptor-1 and TNF-α. The intensity and quantity
of immunostaining were evaluated separately for tumor
cell cytoplasm and tumor cell nucleus. Immunostaining
results were correlated with each other and with patient
survival. All proteins were found to be expressed in the
majority of the tumor cells. The expression (i) of the
following members of TNFR-SF and their ligands
correlated with each other: TNF-Receptor-1 and TNFα
(cytoplasmatic scores, p=0.001), TNF-Receptor 1 and
TRAIL (nuclear antigen expression p=0.005 and the
main score p=0.001, which contains the overall
intracellular antigen expression), TNF-Receptor 1 and
CD95 (main score, p=0.001), TRAIL-Receptor-1 and
TRAIL-Receptor-2 (nuclear parameters, p=0.023), TRAIL-Receptor-4 and TRAIL (main score p=0.041). In
addition (ii), high cytoplasmatic expression of TNFReceptor-1
and a strong cytoplasmatic and nuclear
expression of CD95 correlated significantly with a better
prognosis of the PDAC patients.
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