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Immunohistochemical profiling of liver metastases and matched-pair analysis in patients with metastatic pancreatic ductal adenocarcinoma
Authors:Thomas Held  Caroline S. Verbeke  Oliver Strobel  Wiktor Rutkowski  Christina Villard  Carlos Fernández Moro  Marco Del Chiaro  Markus Büchler  Rainer Heuchel  Matthias Löhr
Affiliation:1. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany;2. Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany;3. National Center for Tumor Diseases (NCT), Heidelberg, Germany;4. Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden;5. Department of Pathology, Karolinska University Hospital, Stockholm, Sweden;6. Institute of Clinical Medicine, University of Oslo, Oslo, Norway;7. Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany;8. Department of Cancer, Karolinska University Hospital, Stockholm, Sweden
Abstract:BackgroundThe purpose of the current study was to investigate the immunohistochemical (IHC) profile of liver metastases (LM) in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsExpression of 15 IHC markers in liver biopsies from 77 patients with PDAC, who were diagnosed between 2010 and 2014, were evaluated. In a separate subgroup analysis (n = 12), paired samples (LM and primary tumor) from the same patient were investigated for IHC profile differences.ResultsLM samples were classified as pancreatobiliary-type (PB-type) in 72 patients (93.5%), intestinal-type (INT-type) in four patients (5.2%), and squamous in one patient (1.3%). There was no significant difference in overall survival (OS) between LM of the PB-type or INT-type (p = 0.097). In a multivariate analysis, age <70 years (p = 0.047), absence of SMAD4 mutation (p = 0.026), absence of CDX2 expression (p = 0.003), and well to moderate differentiation were significant prognostic factors for better OS in patients with LM (p = 0.031). Analysis of paired tissue samples from LM and the primary tumor revealed a difference in CDX2 (50% increase, p = 0.125) and SMAD4 (33% loss of SMAD4, p = 0.375).ConclusionsCDX2 expression and SMAD4 mutation indicate a poor outcome in patients with LM of PDAC. Matched-pair analysis revealed differences in distinct IHC marker expression.
Keywords:Corresponding author. Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, D-69120, Heidelberg, Germany.  Pancreatic cancer  Epithelial-mesenchymal transition  Metastases  CDX2  SMAD4
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