Native and sialic acid masked Lewis(a) antigen reactivity in medullary thyroid carcinoma. Distinct tumour-associated and prognostic relevant antigens.

Abstract

Forty-six medullary thyroid carcinomas (MTC) were subjected to a qualitative and quantitative characterization of native and sialic acid masked Lewis(a) (Le(a)) antigens. Immunohistochemical investigations included monoclonal antibodies (MABs) directed against alpha(2,3)-sialyl-Le(a), i.e. CA19-9 (MAB 19-9), native Le(a) (MAB anti Le(a)) and alpha(2,3)sialyl type 1 structure, i.e. CA 50 (MAB C50). To detect sialic acid masked Le(a) reactivity, MAB anti-Le(a) was also applied to native and enzymatically desialylated tissue sections with and without masking of sialic acid residues by sialic acid and sequence specific lectins. Only 7 MTC (15%) displayed a weak expression of CA19-9, while 16 (33%) showed moderate positive staining for native Le(a). Twenty-seven tumours exhibited a strong staining by the N'ase MAB anti Le(a) staining sequence. The latter could most effectively be inhibited by the simultaneous masking of alpha(2,3)-and alpha-(2,6)-linked sialic acid residues due to the competitive binding of sialic acid and sequence specific lectins: Maackia amurensis agglutinin (specific alpha(2,3)-linked sialic acid) and Sambucus nigra agglutinin (specific alpha(2,6)-linked sialic acid). Thus, in MTC the major portion of sialic acid masked Le(a) antigen reactivity is different from that detected by the MAB 19-9. The antigen reactivity is probably due to Le(a) structures containing both alpha(2,3) and alpha(2,6)-linked sialic acid residues. A highly significant correlation between the expression of CA50 and that detected by the N'ase MAB anti-Le(a) staining sequence indicates that the alpha(2,3)-sialyl type 1 chain represents a common intermediate structure within the pathway of the biosynthesis of sialylated Le(a) antigens, excluding the formation of CA19-9 via the formation of the disialyl type 1 structure. This is subsequently fucosylated to the corresponding sialic acid masked Le(a). Preliminary clinicopathological studies indicate that the sialic acid masked Le(a) antigens detected by the N'ase MAB anti-Le(a) staining sequence are related to biologically aggressive MTC.