An Immunohistochemical Study of Osteopontin in Hepatolithiasis

J Hepatobiliary Pancreat Surg. 2008;15(6):615-21. doi: 10.1007/s00534-007-1320-8. Epub 2008 Nov 7.


Background/purpose: Mucin glycoprotein from the intrahepatic bile ducts, and from the intramural and extramural glandular epithelia, is thought to contribute to the formation of the matrix, or nucleus, in hepatolithiasis and to contribute to biomineralization systems. Osteopontin (OPN), a noncollagenous acidic bone matrix glycoprotein that possesses calcium-binding properties. To investigate the role of OPN in the genesis of hepatolithiasis, OPN was immunohistochemically studied in the intrahepatic bile ducts, intramural and extramural glands, and in stones.

Methods: An immunohistochemical study was performed in 21 human liver specimens with hepatolithiasis, by the EnVision (Dako Japan, Kyoto, Japan) method.

Results: Staining for OPN was strongly positive in the epithelium of stone-laden intrahepatic bile ducts, intramural and extramural glands, and in stones. The stone-laden intrahepatic bile ducts were infiltrated by macrophages showing intense staining for OPN. Sections of the hepatolithiasis, viewed under low magnification, showed a lamellar pattern of OPN immunolabeling, and they showed a reticular pattern under high magnification. In the center of the stones, large nestlike membranous structures were frequently present.

Conclusions: Our result indicates that OPN, an acidic glycoprotein from intrahepatic bile ducts and from intramural and extramural glandular epithelia, seems to be involved in lithiasis, both as a core protein in the early phase, and in the late phase.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Ducts, Intrahepatic / metabolism*
  • Cholelithiasis / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Osteopontin / metabolism*


  • Osteopontin