Loss of TRAIL-receptors is a recurrent feature in pancreatic cancer and determines the prognosis of patients with no nodal metastasis after surgery

• Published in: PloS one 2013-02, Vol.8 (2), p.e56760-e56760
• Main Authors: Gallmeier, Eike, Bader, Dominik C, Kriegl, Lydia, Berezowska, Sabina, Seeliger, Hendrik, Göke, Burkhard, Kirchner, Thomas, Bruns, Christiane, De Toni, Enrico N
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Aged; Antibodies; Antigens; Apoptosis; Cancer; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - surgery; Cell Membrane - metabolism; Clinical trials; Confidence intervals; Evolution & development; Female; Hospitals; Humans; Immunoglobulins; Immunohistochemistry; Kaplan-Meier Estimate; Ligands; Lymph nodes; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic Metastasis - pathology; Male; Medical prognosis; Medical research; Medicine; Metastases; Metastasis; Middle Aged; Pancreas - metabolism; Pancreas - pathology; Pancreatic cancer; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Pathology; Patients; Prognosis; Prostate; Receptors; Receptors, TNF-Related Apoptosis-Inducing Ligand - deficiency; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Regression analysis; Staining; Staining and Labeling; Statistical analysis; Surgery; Surveillance; Tissues; Tumor necrosis factor-TNF; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056760

Agonistic antibodies targeting TRAIL-receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are being developed as a novel therapeutic approach in cancer therapy including pancreatic cancer. However, the cellular distribution of these receptors in primary pancreatic cancer samples has not been sufficiently investigated and no study has yet addressed the issue of their prognostic significance in this tumor entity. Applying tissue microarray (TMA) analysis, we performed an immunohistochemical assessment of TRAIL-receptors in surgical samples from 84 consecutive patients affected by pancreatic adenocarcinoma and in 26 additional selected specimens from patients with no lymph nodes metastasis at the time of surgery. The prognostic significance of membrane staining and staining intensity for TRAIL-receptors was evaluated. The fraction of pancreatic cancer samples with positive membrane staining for TRAIL-R1 and TRAIL-R2 was lower than that of cells from surrounding non-tumor tissues (TRAIL-R1: p