Extracellular matrix proteins, integrin receptors (VLA-β1, VLA-α2 and VLA-α5) and growth fraction in atypical macroregenerative nodules of the liver: an immunocytochemical case study

A case of cirrhotic liver harbouring three atypical macroregenerative nodules and an hepatocellular carcinoma was immunocytochemically investigated for the expression of VLA-β 1, VLA-α2 and VLA-α5 integrins and for different extracellular matrix (ECM) components (collagen I, collagen IV, laminin, fibronectin and tenascin). In addition, the proliferative activity within the nodules was evaluated, using the MIB 1 monoclonal antibody (MAb). The cirrhotic liver disclosed a continuous staining pattern of the ECM proteins investigated, as well as a "sinusoidal" immunostaining of VLA-β1, VLA-α2 and VLA-α5. The macroregenerative nodules showed a discontinued immunoreactivity for ECM proteins while maintaining a VLA-β1 sinusoidal immunostaining, coupled with intercellular immunostaining. VLA-α2 and VLA-α5 expression was lacking. The growth fraction was low in both the above pathological conditions. The hepatocellular carcinoma was devoid of any ECM immunostaining. VLA-β1 immunoreactivity exhibited a honeycomb pattern of staining, whereas VLA α subunits were absent. MIB1 expression was high, being present in 30% of neoplastic nuclei. A possible relationship between atypical macroregenerative nodules and hepatocellular carcinoma is discussed.