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Quantitative and Qualitative Characterization of Human Cancer-associated Serum Glycoprotein Antigens Expressing Epitopes Consisting of Sialyl or Sialyl-Fucosyl Type 1 Chain¹

Departments of Laboratory Medicine [R. K., A. K., S. I., K. Z., K. S.] and Internal Medicine [H. I.], Kyoto University, School of Medicine, Kyoto; Otsuka Assay Institute, Tokushima [T. T., A. N., H. H., M. A., S. S.]; Department of Urology, Tohoku University, School of Medicine, Sendai, Japan [Y. F.]; and Department of Biochemical Oncology, Fred Hutchinson Cancer Research Center, The Biomembrane Institute, and the University of Washington, Seattle, Washington 98119 [R. K., S-i. H.]

The levels of carbohydrate antigens having epitopes consisting of type 1 chain (RGalß1GlcNAcß13Galß1R) in the sera of patients with various malignant and nonmalignant disorders have been investigated with the use of three monoclonal antibodies, N-19-9, FH-7, and FH-9. Serum levels of 23 sialylated Le^a antigen and 26 sialylated Le^a antigen, defined respectively by antibodies N-19-9 and FH-7, were found to be frequently high in patients with cancer of the digestive system, particularly pancreatic cancer. High levels of 23,26 disialylated Lc₄ antigen, defined by antibody FH-9, were less frequent in cancer patients when compared with the other two antigens. In patients with nonmalignant disorders, especially renal and autoimmune diseases, serum levels of the two type 1 chain antigens defined by FH-7 and FH-9 were more frequently high than that defined by N-19-9. Molecular weights and other general biochemical characteristics of serum mucin carrying the type 1 chain determinants were not significantly different in cancer patients as compared with patients with nonmalignant disorders. However, the degree of glycosylation of the antigen, as assessed by its solubility in perchloric acid, showed significant differences; i.e., the mucin antigen carrying 26 sialylated Le^a determinant in the sera of patients with nonmalignant disorders had the highest carbohydrate/protein ratio, followed by the mucin carrying the same determinant in the sera of cancer patients. Mucin antigen carrying 23 sialylated Le^a antigen or 23, 26 disialylated Lc₄ antigen in cancer patients had the lowest carbohydrate/protein ratio among the four groups tested. Thus, the carbohydrate/protein ratio in the type 1 chain mucin antigens in sera of normal subjects is higher than that in sera of cancer patients (P < 0.05). This finding is in contrast to previous findings on the mucin antigens carrying the type 2 chain determinant (R. Kannagi et al., Cancer Res., 46: 2619–2626, 1986), in which the mucin antigen in cancer patients was found to have a much higher carbohydrate/protein ratio than that carrying the same antigenic determinants in patients with nonmalignant disorders.

¹ This investigation has been supported in part by grants from Otsuka Pharmaceutical Company and the United States National Cancer Institute Outstanding Investigator Grant CA42505 (to S-i. H.), as well as by grants from the Ministry of Education, Government of Japan (to R. K.).

Received 10/23/87. Revised 3/11/88. Accepted 3/29/88.

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