Focal nodular hyperplasia of the liver: composition of the extracellular matrix and expression of cell-cell and cell-matrix adhesion molecules.
We studied by immunohistochemistry 25 cases of focal nodular hyperplasia (FNH) to evaluate the composition of the extracellular matrix and the expression and distribution of endothelial cell-cell adhesion molecules and integrin receptors. The extracellular matrix of FNH retained the overall organization of that of normal liver. The matrix of central scars resembled that of portal tracts. The main difference was the presence of large vitronectin deposits, which might indicate the existence of local hemodynamic disturbances. The matrix lining the sinusoid-like vessels running in the hyperplastic parenchyma retained characteristic features of the normal perisinusoidal matrix, such as the presence of tenascin. In the zone surrounding the central scars, it contained large amounts of laminin, von Willebrand factor, and thrombospondin, suggesting the development of perisinusoidal fibrosis. Laminin deposition was accompanied by the induction of cell-cell adhesion molecules on adjacent endothelial cells and by the up-regulation of specific integrin receptors on both hepatocytes and sinusoidal endothelial cells. In conclusion, our study: (1) reinforces the hypothesis that FNH is merely a hyperplastic response of liver parenchyma to local vascular abnormalities, and (2) shows that the lesions of perisinusoidal fibrosis associated with FNH are accompanied by the induction of integrin receptors on hepatocytes and sinusoidal endothelial cells.
Scoazec
J Y
JY
Laboratoire de Biologie Cellulaire, Université Denis Diderot, Paris, France.
Flejou
J F
JF
D'Errico
A
A
Couvelard
A
A
Kozyraki
R
R
Fiorentino
M
M
Grigioni
W F
WF
Feldmann
G
G
D000328:Adult; D000368:Aged; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000737:chemistry / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D016023:Integrins / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016023:Integrins