NATIVE AND SIALIC-ACID MASKED LEWIS(A) ANTIGEN REACTIVITY IN MEDULLARY-THYROID CARCINOMA - DISTINCT TUMOR-ASSOCIATED AND PROGNOSTIC RELEVANT ANTIGENS

Forty-six medullary thyroid carcinomas (MTC) were subjected to a quali tative and quantitative characterization of native and sialic acid mas ked Lewis(a) (Le(a)) antigens. Immunohistochemical investigations incl uded monoclonal antibodies (MABs) directed against alpha(2,3)-sialyl-L e(a), i.e. CA19-9 (MAB 19-9), native Le(a) (MAB anti Le(2)) and alpha( 2,3) sialyl type 1 structure, i.e. CA 50 (MAB C50). To detect sialic a cid masked Le(a) reactivity, MAB anti-Le(a) was also applied to native and enzymatically desialylated tissue sections with and without maski ng of sialic acid residues by sialic acid and sequence specific lectin s. Only 7 MTC(15%) displayed a weak expression of CA19-9, while 16 (33 %) showed moderate positive staining for native Le(a). Twenty-seven tu mours exhibited a strong staining by the N'ase MAB anti Le(a) staining sequence. The latter could most effectively be inhibited by the simul taneous masking of alpha(2,3) and alpha-(2,6)-linked sialic acid resid ues due to the competitive binding of sialic acid and sequence specifi c lectins: Maackia amurensis agglutinin (specific alpha(2,3)-linked si alic acid) and Sambucus nigra agglutinin (specific alpha(2,6)-linked s ialic 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 s ignificant correlation between the expression of CA50 and that detecte d by the N'ase MAB anti-Le(a) staining sequence indicates that the alp ha(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 ty pe 1 structure. This is subsequently fucosylated to the corresponding sialic acid masked Le(a). Preliminary clinicopathological studies indi cate that the sialic acid masked Le(a) antigens detected by the N'ase MAB anti-Le(a) staining sequence are related to biologically aggressiv e MTC.