Enhanced tenascin expression correlates with inflammation in primary sclerosing cholangitis

Tenascin (Tn) is an extracellular matrix (ECM) glycoprotein upregulated during development, repair and oncogenesis. In the normal adult liver, Tn is limited to vessels and, focally, to sinusoidal walls. In this study, samples were obtained from 12 livers removed during transplantation for primary sclerosing cholangitis (PSC). Paraffin sections were immunostained with monoclonal antibodies BC-4 which recognizes all isoforms of Tn and alpha-SMA-1 to alpha smooth muscle actin (alpha-SMA). Intense Tn reactions were noted in areas of ductular proliferation and inflammation at the parenchyma-stroma interface. In the absence of ductular proliferation, no selective Tn upregulation was noted. Staining was preferentially located adjacent to ductular basement membranes, with minimal extension into the surrounding ECM. Advanced histologic stages with micronodules rimmed by proliferating ductules showed the most florid Tn reactions, whereas fibrous septa and edematous perinodular haloes did not react. Increased periductal Tn was also seen associated with active inflammation, notably around large, dilated septal ducts, while fibro-obliterative ductal lesions and "onion skin fibrosis" did not stain. Focally enhanced Tn staining was noted in sinusoids neighboring ductular proliferation, and in dilated sinusoids within cirrhotic nodules. Reactions with alpha-SMA-1 highlighted myofibroblasts and activated Ito cells in topographic association with Tn reactions. We conclude that Tn is upregulated in PSC where it is preferentially localized in the remodeling matrix encompassing proliferating ductules and in altered periductal matrix. Our results suggest that Tn determinations in tissue or serum samples might be helpful in the clinical assessment of "activity" in PSC.