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From the Institut National de la Santé et de la Recherche
Médicale U-370 and Liver Unit,*
Centre Hospitalier
Universitaire Necker, Paris, France; the Service d’Anatomie et de
Cytologie Pathologiques,
Hôpital Antoine
Béclère Clamart, France; the Service
d’Anatomo-pathologie,
Hôpital Laennec,
Paris, France; the Service
d’Hépatologie,§
Hôpital
Necker-Enfants Malades, Paris, France; the Service de Chirurgie
Générale et Digestive,¶
Hôpital
Antoine Béclère, Clamart, France; and the Laboratory for
Histo- and Cytochemistry,||
University of Leuven,
Leuven, Belgium
Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) gene was identified because of its increased expression in 25% of human hepatocellular carcinoma. HIP/PAP protein, a C-type lectin, binds laminin, acts as an adhesion molecule for hepatocytes, and has also been described as an acute phase secretory protein during acute pancreatitis in humans and rats. We investigated HIP/PAP protein expression in patients with various liver diseases associated with ductular reaction. At the same time, we analyzed 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 carcinoma, but was also detected in cholangiocarcinoma cells as well as in reactive non-malignant bile ductules. In contrast, HIP/PAP protein expression was undetectable in normal mature hepatocytes, but some ductular cells localized at the interface of portal tracts with parenchyma were HIP/PAP immunoreactive in normal liver. Finally, we present evidence that HIP/PAP serum levels 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 cholangiolar differentiation and proliferation.
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