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Le^x and Le^y Antigen Expression in Human Pancreatic Cancer¹

Gastrointestinal Research Laboratory (151-M2), Veterans Administration Medical Center and the Department of Medicine, University of California, San Francisco, California 94143 [M. Y., S. H. I., Y. S. K.]; First Department of Surgery, Osaka City University Medical School, Osaka 545, Japan [Y. S. C., K. S., K. U.]; and Division of Biochemical Oncology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104 [S. H.]

Carbohydrate antigens are useful markers for the serological detection of pancreatic cancer. However, data concerning the expression of structurally well-defined carbohydrate antigens in normal and malignant pancreatic tissue is quite limited. The Le^x and Le^y antigens are closely related carbohydrate antigens synthesized on type 2 blood group oligosaccharide side chains of glycolipids and glycoproteins. Monoclonal antibodies anti-SSEA-1 and AH6 recognize "simple" Le^x and Le^y epitopes, respectively, regardless of the length of the carrier carbohydrate. Other monoclonal antibodies recognize Le^x (FH4), sialyl Le^x (FH6, IB9) or Le^y (KH1, CC-1, CC-2) carried only by elongated type 2 side chains with or without internal 1,3 fucosyl substitution. The present comparative immunohistochemical study used tissues of normal pancreas, chronic pancreatitis, and pancreatic cancer to determine the normal expression of Le^x and Le^y antigens in the pancreas and to elucidate any cancer-associated alterations. Le^x-related antigens were not expressed in normal pancreas, expressed in only 10–20% of chronic pancreatitis tissues, but expressed in 50–70% of pancreatic cancer tissues. The frequency of Le^x-related antigen expression in pancreatic cancer tissues was lowest in poorly differentiated cancers. Within a given specimen, at least three or all four of the Le^x recognizing monoclonal antibodies were simultaneously expressed. Unlike Le^x antigens, Le^y-related antigens were expressed in 32–77% of specimens of normal pancreas, with similar frequencies in specimens of chronic pancreatitis and pancreatic cancer. In normal pancreas, simple Le^y was expressed by both ductal and acinar cells, but extended Le^y antigens were expressed only by acinar cells. In pancreatic cancer, extended Le^y antigen expression was found in less than 10% of poorly differentiated tumors. Coexpression among the Le^y-related antigens was less common than with the Le^x-related antigens. Also in cancer specimens, simple Le^x and simple Le^y antigens were often concordantly expressed, whereas extended Le^x and extended Le^y antigen expression was often discordant. Hyperplastic ducts and ductules associated with pancreatic cancer expressed Le^x-related antigens more frequently than morphologically similar lesions associated with chronic pancreatitis. These results demonstrate that Le^x-related antigens are cancer-associated determinants in the human pancreas. The discrepant expression between Le^x and Le^y antigens in these tissues implies altered regulation of fucosyltransferase activity associated with the malignant state.

¹ This work was supported in part by National Cancer Institute Grant CA24321 [Y. S. K.], Public Health Service Grant R01-CA42981-01 awarded by the National Cancer Institute, Department of Health and Human Services [S. H. I.], and OIG1-R35-CA42505 [S. H.]; by the Veterans Administration Medical Research Service [M. Y., S. H. I., Y. S. K.]; by a Veterans Administration Medical Investigator Award [Y. S. K.]; and by a Veterans Administration Research Associate Award [S. H. I.].

² To whom requests for reprints should be addressed, at GI Research Lab (151-M2), Veterans Administration Medical Center, 4150 Clement Street, San Francisco, CA 94121.

Received 7/20/87. Revised 10/15/87. Accepted 10/19/87.

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