Immunohistochemical localization of ganglioside components in hepatocellular carcinoma and liver cirrhosis using monoclonal antibody.

BACKGROUND

In our previous studies (1, 2) a remarkable difference in the patterns of gangliosides was demonstrated between normal human liver and hepatocellular carcinoma (HCC) on thin layer chromatography, consisting of a marked increased in GM2 and the unidentified gangliosides. The proliferation of the unidentified gangliosides was also revealed in certain types of liver cirrhosis. The precise chemical structure of the unidentified components still remains to be elucidated, and there are no comprehensive data on these components investigated in liver tissue from patients with liver cirrhosis, HCC, or malignancies of the biliary and gastrointestinal tracts. In view of this, we studied the immunohistochemical localization of these ganglioside components in these tissues.

EXPERIMENTAL DESIGN

Two unidentified gangliosides were extracted and monoclonal antibody were prepared. Localization of these gangliosides on tissue sections of liver obtained from HCC and liver cirrhosis, and malignancies of the biliary and gastrointestinal tracts was investigated by performing immunohistochemical staining using monoclonal antibody. The carbohydrate composition and sialic acid species of these components were determined by gas-liquid chromatography analysis. The sialic acid linkage to the terminal moiety of these components was also investigated by sialidase treatment.

RESULTS

Staining with monoclonal antibody against specific gangliosides revealed dense brown granules in HCC tissue sections, whereas normal liver, kidney, and spleen sections were negative. Tissue sections of cirrhotic livers generally stained weakly except one case that showed slight to moderate staining. These antigens were immunohistochemically negligible in sections from one case each of gastric, colon, and common bile duct cancer. The ganglioside components identified in HCC were confirmed to be sialosylparagloboside with an alpha 2-6galactosyl terminus as determined by gas-liquid chromatography analysis and enzymatic hydrolysis with different sialidases.

CONCLUSIONS

These components may be a useful marker in the detection of HCC and for subclassification of HCC from the standpoint of ganglioside metabolism.