Keratin 19 marks poor differentiation and a more aggressive behaviour in canine and human hepatocellular tumours

The expression of hepatocellular differentiation (HepPar-1), biliary/progenitor cell (K7, K19), and malignancy (glypican-3) markers was semi-quantitatively assessed by immunohistochemistry. The histological grade of tumour differentiation was determined according to a modified classification of Edmondson and Steiner; the staging included intrahepatic, lymph node or distant metastases. Four of the 34 canine hepatocellular neoplasias showed K19 positivity (12%), of which two co-expressed K7. K19 positive tumours did not express HepPar-1, despite the histological evidence of a hepatocellular origin. Like in human HCC, all K19 positive hepatocellular neoplasias were glypican-3 positive and histologically poorly differentiated and revealed intra- or extrahepatic metastases whereas K19 negative hepatocellular neoplasias did not.K19 positive hepatocellular neoplasias are highly comparable to man and occur in 12% of canine hepatocellular tumours and are associated with a poorly differentiated histology and aggressive tumour behaviour.Hepatic progenitor cells (HPCs) are activated in the majority of liver diseases and are a potential cell of origin for hepatocellular carcinoma (HCC) [1,2]. HCC is a neoplasm of increasing incidence worldwide and is the fifth leading cause of death on a worldwide basis in man [3,4]. Although remarkable advances in surgical and imaging modalities have improved the prognosis of HCC patients [5], the high incidence of intrahepatic recurrence remains a major challenge in HCC therapy [6,7]. In man the only potentially curative modality for HCC is surgical resection (including whole organ transplantation), yet recurrence rates are high and the long-term survival is poor [8]. An additional dilemma is the limited availability of healthy donor livers. Thus, the ability to predict individual recurrence risk and subsequently prognosis would help guide surgical and chemotherapeutic treatment. As the understanding of hepatocarcinogenesis increases, the innu