The most interesting perspective is when these markers will also determine the applicability of tailored therapy for which the dog would fit as a highly relevant model. Conclusions K19 positive hepatocellular neoplasias occur in twelve percent of hepatocellular neoplasias Temsirolimus chemical structure and are associated with a poorly differentiated histology and more aggressive tumour behaviour. K19 expression correlates with the expression of glypican-3 and with the disappearance of the hepatocyte marker HepPar-1

and are valuable clinicopathological and prognostic markers in the histopathological diagnosis of hepatocellular tumours in dogs. K19 positive tumours are highly comparable in histology, marker expression, and prevalence to their human counterparts thus advocating the dog as a model for future anti-tumour treatment. Methods Samples For this study paraffin material of a wide variety of primary liver tumours was available from the paraffin material archive present at the department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University (dog, n = 20), Valuepath, Laboratory for Veterinary Z-IETD-FMK order Pathology, Hoensbroek, The Netherlands (dog, n = 19), and University Hospitals Leuven, Leuven, CUDC-907 nmr Belgium (man, n = 8). In addition, frozen material (dog, n = 7) was available from the tissue bank present at the Department of Clinical Sciences of Companion Animals,

Faculty of Veterinary Medicine, Utrecht University. All the material was derived from patients who were submitted for individual diagnostic purposes; no tissue was taken purposely for the reported study. Healthy canine liver samples embedded in paraffin were also available from the Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University derived from non-liver related research. As a positive control paraffin-embedded liver tissue samples from dogs with fulminant hepatitis and reactive ductular proliferation of HPCs were used (courtesy Dr. J. IJzer, Department of Pathobiology, Faculty of Nitroxoline Veterinary Medicine, Utrecht University). All liver tumour samples and fulminant hepatitis samples were fixed in 10% neutral

buffered formalin and routinely embedded in paraffin. The paraffin sections (4 μm) were mounted on poly-L lysine coated slides. All the sections (4 μm) were stained with haematoxylin and eosin (HE) for histological determination. To exclude hepatic carcinoids in this study, the following neuro-endocrine differentiation markers were used; chromogranin-A, neuron-specific enolase, and synaptophysin, data not shown [41–43]. Grading Histological grading of malignant tumours is based on the grading system of Edmondson and Steiner (ES grading system). The ES grading uses a scale of one to four, with increasing nuclear irregularity, hyperchromatism and nuclear/cytoplasmic ratio, associated with decreasing cytological differentiation for each successively higher grade.