Background: N-Acetylneuraminic acid and N-glycolylneuraminic acid (NeuGc) are the most common sialic acids in mammals, and NeuGc has attracted attention as a tumor-associated antigen.
Methods: In frozen liver sections from patients with hepatocellular carcinoma, glycolipid-type NeuGc was detected on the surface of liver cancer cells in 9 of 17 samples (52.9%) by immunostaining, using two chicken monoclonal antibodies against NeuGc and the tyramide signal amplification method. When conventional immunostaining without amplification was used, all 17 specimens tested were negative.
Results: Increased serum levels of anti-NeuGc IgG and/or IgM were observed in 13 of the 17 patients with hepatocellular carcinoma (76.5%). The presence of these antibodies was mostly attributed to the expression of NeuGc on hepatocellular carcinoma cells. Of the subjects with small HCCs (diameter 3 cm or less), 6 of 10 were positive for serum anti-NeuGc antibodies; however, 1 of these was negative for both serum Alpha-fetoprotein (AFP) and for prothrombin-induced vitamin K antagonist II (PIVKA-II). There was no correlation between serum AFP- or PIVKA-II, levels and the presence of NeuGc or anti-NeuGc IgG and/or IgM.
Conclusion: The tyramide signal amplification method is useful for the immunohistochemical detection of low-level NeuGc expression by hepatocellular carcinoma cells. We therefore consider that measurement of serum levels of anti-NeuGc antibodies is clinically meaningful and that anti-NeuGc antibody may be a useful screening test, in combination with AFP and PIVKA-II, for the early diagnosis of hepatocellular carcinoma.