Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers

Medullary thyroid carcinoma (MTC) accounts for only 1-2% of thyroid cancers; however, metastatic MTC is a mortal disease with no cure. In this study, glycosphingolipids were isolated from human MTCs and characterized by mass spectrometry and binding of carbohydrate recognizing ligands. The tissue distribution of selected compounds was investigated by immunohistochemistry. The amount of acid glycosphingolipids in the MTCs was higher than in the normal thyroid glands. The major acid glycosphingolipid was the GD3 ganglioside. Sulfatide and the gangliosides GM3 and GD1a were also present. The majority of the complex non-acid glycosphingolipids had type 2 (Gal beta 4GlcNAc) core chains, i.e., the neolactotetraosylceramide, the Le(x), H type 2 and x(2) pentaosylceramides, the Le(y) and A type 2 hexaosylceramides, and the A type 2 heptaosylceramide. There were also compounds with globo (Gal alpha Gal beta 4Glc) core, i.e., globotriaosylceramide, globotetraosylceramide, the Forssman pentaosylceramide, and the Globo H hexaosylceramide. Immunohistochemistry demonstrated an extensive expression av Le(y) in the MTC cells and also a variable intensity and prevalence of Globo H and Le(x). One individual with multiple endocrine neoplasia type 2B expressed the Forssman determinant, which is rarely found in humans. This study of human MTC glycosphingolipids identifies glycans that could serve as potential tumor-specific markers.

Automated summary

The study found higher levels of acid glycosphingolipids in human MTCs and identified potential tumor-specific markers; Immunohistochemistry showed extensive expression of Le(y) in MTC cells, as well as variable intensity and prevalence of Globo H and Le(x); One individual with multiple endocrine neoplasia type 2B expressed the rare Forssman determinant.