Native and sialic acid masked Lewis^a antigen reactivity in medullary thyroid carcinoma

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 comptetitive 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.