Native and sialic acid masked Lewis(a) antigen reactivity in medullary thyroid carcinoma. Distinct tumour-associated and prognostic relevant antigens.
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.
Vierbuchen
M
M
Department of Pathology, General Hospital St. Georg, Hamburg, Germany.
Schröder
S
S
Larena
A
A
Uhlenbruck
G
G
Fischer
R
R
D000911:Antibodies, Monoclonal; D000941:Antigens / Q000032:analysis*; D002236:Carbohydrate Conformation; D018276:Carcinoma, Medullary / Q000276:immunology*; D005690:Galactose / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D037102:Lectins; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000378:metabolism; D010835:Phytohemagglutinins; D037121:Plant Lectins; D011379:Prognosis; D054788:Ribosome Inactivating Proteins; D012794:Sialic Acids / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D037102:Lectins; D007983:Lewis Blood Group Antigens; D010835:Phytohemagglutinins; D037121:Plant Lectins; C050600:Sambucus nigra lectins; D012794:Sialic Acids; C100156:leukoagglutinins, plants; D009439:Neuraminidase; D054788:Ribosome Inactivating Proteins; D019158:N-Acetylneuraminic Acid; D005690:Galactose