Several studies show that a cut-off of five percent K19 positive cells already influences the outcome of the patient [12]. These studies in man validate K19 as a clinically meaningful and prognostically relevant marker for hepatocellular carcinoma. Other recently described markers include glypican-3 (GPC3) which is an extracellular proteoglycan that is inferred to play an important role in growth control in embryonic mesodermal tissues in which it is selectively expressed [19]. GPC3 is a member of the glypican family of glucosyl-phosphatidylinositol-anchored cell-surface heparin sulfate proteoglycans and is Fer-1 price well established as a serologic

and immunohistochemical diagnostic tool for hepatocellular carcinomas in man. The presence of GPC3 (mRNA and immuno-histochemistry) is much higher in hepatocellular carcinomas compared to cirrhotic tissue or small focal lesions, indicating that the transition from small premalignant lesions to hepatocellular carcinomas is associated with a sharp increase of GPC3 expression in the majority of cases [20, 21]. In view of the similarities in cell biological mechanisms involved in

regeneration buy PKC412 and tumour development between human liver Selleck ARRY-162 tumours and liver tumours in small domestic animals, it is conceivable that these acquisitions found in human hepatic tumour pathology may also be true for the canine liver tumours [22]. To this date, no mouse models exist which resemble K19 positive HCCs in man. Therefore clinicopathological prognostic markers including marker expression of K7, K19 (HPC and cholangiocytes), HepPar-1 (hepatocytes) and glypican-3 (malignant HCC) were examined in primary liver tumours of dogs and compared to man. Results indicate a high similarity in histopathology of primary liver tumours between man and dog, emphasizing the use of dogs as possible treatment models. Results Histological classification of canine primary liver tumours Liver material of 46 dogs

was included in this study (male to female ratio: 0.7). Breeds represented included mixed breed, Flat coated retriever, Airedale terrier, German Sheppard, ioxilan Alaskan malamute, Pit bull, Maltezer, Cocker spaniel, Appenzeller, Golden retriever and Yorkshire terrier. The age range was six to fourteen years. Microscopical examination (Table 1) classified the 46 primary liver tumours as: four nodular hyperplasia (9%) and 34 hepatocellular tumours (74%). Five hepatic carcinoids (11%) positive for one or more neuro-endocrine differentiation markers (chromogranin-A, neuron-specific enolase, and synaptophysin) and three cholangiocellular carcinomas (7%) were not further analysed in this study. Apart from the neoplastic changes, no additional liver pathology was seen in any of the dogs. Healthy liver tissue was added as a control. Hepatocellular tumours were classified in different groups based on K19 positivity.