Native and sialic acid masked Lewisa antigen reactivity in medullary thyroid carcinoma |
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Authors: | M. Vierbuchen S. Schröder G. Uhlenbruck A. Lavena R. Fischer |
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Affiliation: | (1) Department of Pathology, General Hospital St. Georg, Lohmühlenstrasse 5, D-20099 Hamburg, Germany;(2) Institute of Pathology, University of Hamburg, Hamburg, Germany;(3) Institute of Immunobiology, University of Cologne, Cologne, Germany;(4) Institute of Pathology, University of Cologne, Cologne, Germany |
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Abstract: | Forty-six medullary thyroid carcinomas (MTC) were subjected to a qualitative and quantitative characterization of native and sialic acid masked Lewisa (Lea) antigens. Immunohistochemical investigations included monoclonal antibodies (MABs) directed against alpha(2,3)-sialyl-Lea, i.e. CA19-9 (MAB 19-9), native Lea (MAB anti Lea) and alpha(2,3) sialyl type 1 structure, i.e. CA 50 (MAB C50). To detect sialic acid masked Lea reactivity, MAB anti-Lea 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 Lea. Twenty-seven tumours exhibited a strong staining by the N'ase MAB anti Lea 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 Lea antigen reactivity is different from that detected by the MAB 19-9. The antigen reactivity is probably due to Lea 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-Lea 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 Lea 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 Lea. Preliminary clinicopathological studies indicate that the sialic acid masked Lea antigens detected by the N'ase MAB anti-Lea staining sequence are related to biologically aggressive MTC. |
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Keywords: | Lewisa blood group antigens Carbohydrate histochemistry Medullary thyroid carcinoma Sialic acid specific lectins Tumour associated antigens |
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