Gk. Koukoulis et al., Enhanced tenascin expression correlates with inflammation in primary sclerosing cholangitis, PATH RES PR, 195(11), 1999, pp. 727-731
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.