Protein expression of double-stranded RNA-activated protein kinase (PKR) in intrahepatic bile ducts in normal adult livers, fetal livers, primary biliary cirrhosis, hepatolithiasis and intrahepatic cholangiocarcinoma

Background/Aim: The protein expression of double-stranded RNA-activated pro tein kinase (PKR) in intrahepatic bile ducts has not been investigated. Met hods: Immunohistochemistry and a semiquantitative scoring method in normal liver and biliary diseases were used for the investigation. Results. In "no rmal" adult livers (n=10), intrahepatic bile ducts were negative for PKR. I n normal fetal livers (n=25), primitive biliary epithelia were almost negat ive for PKR. In primary biliary cirrhosis (PBC) (n=30), damaged bile ducts were frequently positive for PKR, while uninvolved bile ducts were negative . In hepatolithiasis (n=27), proliferated bile ducts were positive for PKR, and the PKR score correlated with the degree of proliferation. In cholangi ocarcinoma (CC) (n=44), PKR expression was frequently noted, and the PKR sc ore correlated with good differentiation of CC, being highest in well-diffe rentiated CC and lowest in poorly-differentiated CC. The PKR score decrease d in the following order: CC (mean PKR score=3.96), hepatolithiasis (2.56), PBC (1.60), normal fetal liver (0.40), and normal adult livers (0.00). The PKR expression in hepatocytes was "baseline" in normal adult livers, while moderately increased in fetal livers, PBC, hepatolithiasis and CC. Conclus ions: Although the significance of these data is unclear, they suggest (i) that PKR is absent in bile ducts in normal adult and fetal livers, (ii) tha t PKR in bile duct cells newly emerges or increases in PBC, hepatolithiasis , and CC, (iii) that PKR accumulates in damaged bile ducts in PBC, (iv) tha t PKR increases in parallel with biliary cell proliferation in hepatolithia sis, and (v) that PKR expression correlates with differentiation in CC. PKR expression in intrahepatic bile ducts seems to be associated with inflamma tion or cell proliferation of the bile duct cells.