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The expression of death receptor systems TRAIL-R1/-R2/-R4, CD95 and TNF-R1 and their cognate ligands in pancreatic ductal adenocarcinoma.

The expression of five members of the TNF receptor superfamily and two of their ligands in human pancreatic ductal adenocarcinoma were investigated in parallel 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 TNF-Receptor-1 and a strong cytoplasmatic and nuclear expression of CD95 correlated significantly with a better prognosis of the PDAC patients.