Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP)is expressed and secreted by proliferating ductules as well as by hepatocarcinoma and cholangiocarcinoma cells

Hepatocarcinoma-intestine-pancreas/pancreatic associated protein. (HIP/PAP) gene was identified because of its increased expression in 25% of human he patocellular carcinoma. HIP/PAP protein, a C-type lectin, binds laminin, ac ts as an adhesion molecule for hepatocytes, and has also been described as an acute phase secretory protein during acute pancreatitis in humans and ra ts. We investigated HIP/PAP protein expression in patients with various liv er diseases associated with ductular reaction. At the same time, we analyze d patients with hepatocellular carcinoma and cholangiocarcinoma, and tested HIP/PAP protein levels in sera to establish the pattern of secretion. Our data show that HIP/PAP expression was not restricted to hepatocellular carc inoma, but was also detected in cholangiocarcinoma cells as well as in reac tive non malignant bile ductules. In contrast, HIP/PAP protein expression w as undetectable in normal mature hepatocytes, but some ductular cells local ized at the interface of portal tracts with parenchyma were HIP/PAP immunor eactive in normal Liver. Finally, we present evidence that HIP/PAP serum le vels were increased in 21/28 (75%) patients with hepatocellular carcinoma, and in 25/51 (49%) patients with nonmalignant cirrhosis, Altogether, these results suggest that HIP/PAP protein may be implicated in hepatocytic and c holangiolar differentiation and proliferation.