Enhanced tenascin expression correlates with inflammation in primary sclerosing cholangitis

Tenascin (Tn) is an extracellular matrix (ECM) glycoprotein upregulated dur ing development, repair and oncogenesis, In the normal adult liver, Tn is l imited to vessels and, focally, to sinusoidal walls. In this study, samples were obtained from 12 livers removed during transplantation for primary sc lerosing cholangitis (PSC). Paraffin sections were immunostained with monoc lonal antibodies BC-4 which recognizes all isoforms Of Tn and alpha-SMA-1 t o 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 upregu lation was noted. Staining was preferentially located adjacent to ductular basement membranes, with minimal extension into the surrounding ECM. Advanc ed histologic stages with micronodules rimmed by proliferating ductules sho wed the most florid Tn reactions, whereas fibrous septa and edematous perin odular haloes did not react. Increased periductal Tn was also seen associat ed with active inflammation, notably around large, dilated septal ducts, wh ile fibro-obliterative ductal lesions and "onion skin fibrosis" did not sta in. Focally enhanced Tn staining was noted in sinusoids neighboring ductula r proliferation, and in dilated sinusoids within cirrhotic nodules, Reactio ns with alpha-SMA-1 highlighted myofibroblasts and activated Ito cells in t opographic association with Tn reactions. We conclude that Tn is upregulated in PSC where it is preferentially locali zed in the remodeling matrix encompassing proliferating ductules and in alt ered periductal matrix. Our results suggest that Tn determinations in tissu e or serum samples might be helpful in the clinical assessment of "activity " in PSC.