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Tumor-associated Sialylated Antigens Are Constitutively Expressed in Normal Human Colonic Mucosa¹

Gastrointestinal Research Laboratory, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029 [S. O., I. H., A. C., D. D., J. M., S. H. I.], and The Biomembrane Institute, University of Washington, Seattle, Washington 98119 [A. S., S. H.]

Immunohistochemical studies have indicated that sialylated carbohydrate antigens such as sialyl-Tn, sialyl-Leⁿ, and sialyl-Le^x are expressed in a tumor-associated fashion in human colon. Since sialic acid residues are O-acetylated more extensively in normal colonic epithelium than in colon cancer cells, we examined whether deacetylation of colonic tissues might enable monoclonal antibodies to recognize these tumor-associated sialylated antigens. In normal colon, deacetylation turned most cases (82%) positive with anti-sialyl-Tn mAb TKH2; and in colon cancers, it increased the number of TKH2-positive cells. Sialyl-Leⁿ and sialyl-Le^x detection was also increased after deacetylation of normal and malignant colonic tissues so that the frequency of positive cases in normal tissues was similar to that in the cancers. However, in the stomach and pancreas, the same treatment rarely increased the detection of the sialylated epitopes in normal or cancerous tissues. Thus, the same sialylated epitopes can be expressed in a tumor-associated fashion by different mechanisms in different gastrointestinal organs; in the colon, these antigens are constitutively expressed and O-acetylated, whereas in the upper gastrointestinal tract, they are rarely O-acetylated, suggesting that other mechanisms such as differences in glycosylation account for the cancer-associated expression.

¹ Supported in part by USPHS Grant CA52491 from the National Cancer Institute (to S. H. I.) and The Chemotherapy Foundation. S. H. I. is the recipient of an Irma T. Hirschl Charitable Scholar Award.

² To whom requests for reprints should be addressed, at GI Division, Box 1069, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York City, NY 10029.

Received 11/15/94. Accepted 2/28/95.

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