Using
monoclonal antibodies (MoABs) against
blood group determinants and related carbohydrate sequences, it is now possible to clarify their
carcinoma-associated modulation at a molecular level. In the present study a panel of MoABs against different type 1 chain derived
blood group antigens, comprising A, B, H type 1, Le(a),
sialyl-Le(a) (CA 19-9), sialyl type 1 structure (CA 50), and Le(b) was used to investigate their immunoreactivity in 38
medullary carcinomas of the thyroid (MTC) and in normal thyroid tissue. The
antigens were not expressed in normal follicular or C-cells but were expressed to a various extent in MTC. The studies revealed some characteristic anomalies in the frequency and patterns of
tumor-associated
antigen expression. The MoAB C 50 stained 32 of the 38
tumors, H type 1 (Le(d)) was demonstrated in 21 and the
Le(b) antigen in 27. The Le(a)- and the A
antigen were detected in 10 and 12
tumors and the B
antigen in one. From the results some rules about the pathways for
tumor-associated re-expression of these
antigens can be deduced. Le(a)
antigen expression was significantly correlated with the CA 50 and Le(b)
antigens. The significant relation observed between A-, H1-, and
Le(b) antigen formation in MTC suggests the existence of a
carcinoma-associated
fucosyltransferase committing the type 1 precursor chain along the H1-antigen pathway, and by further glycosylation to an A-, B-, or a
Le(b) antigen. Comparative studies of
tumor-associated H type 1 and H type 2
antigen expression revealed that H type 2
antigen synthesis was significantly related to a blood type 0 in the host. On the other hand, H1
antigen reactivity was independent of the AB0 blood type of the hosts and was also detected in H type 2
antigen-negative
tumors. These findings support the proposal that even in
tumor tissue,
H antigen expression is still determined by the interaction of at least two different genes. Despite the occurrence of the precursor substance (CA 50) and the formation of the Le(a)- and Le(b)
antigens, indicating the presence of a alpha 1,4-fucosyl-transferase (Lewis-
enzyme), only two
tumors showed the formation of CA 19-9. In conclusion, the investigations demonstrated the dominant re-expression of three type 1 chain-derived structures in MTC, namely H type 1, Le(b), and CA 50. These findings support the general concept demonstrated in other
carcinomas, that fucosyl- and
sialyltransferases are preferentially activated in MTC.(ABSTRACT TRUNCATED AT 400 WORDS)