Characterization of human medullary thyroid carcinoma glycosphingolipids identifies potential cancer markers

Abstract

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 recogniz-ing ligands. The tissue distribution of selected compounds was investigated by immunohistochem-istry. 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 (Galβ4GlcNAc) core chains, i.e., the neolactotetraosylceramide, the Lex, H type 2 and x2 pen-taosylceramides, the Ley and A type 2 hexaosylceramides, and the A type 2 heptaosylceramide. There were also compounds with globo (GalαGalβ4Glc) core, i.e., globotriaosylceramide, glo-botetraosylceramide, the Forssman pentaosylceramide, and the Globo H hexaosylceramide. Im-munohistochemistry demonstrated an extensive expression av Ley in the MTC cells and also a var-iable intensity and prevalence of Globo H and Lex. One individual with multiple endocrine neo-plasia 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.