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ß1–6 Branched Oligosaccharides as a Marker of Tumor Progression in Human Breast and Colon Neoplasia¹

Department of Pathology, Mount Sinai Hospital, Toronto, Ontario [B. F., M. A.]; Faculty of Medicine [B. F., M. A.] and Department of Medical Genetics [M. D., J. W. D.], University of Toronto, Toronto, Ontario; and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5 [U. S., M. D., J. W. D.]

Malignant transformation of murine and human cells is commonly associated with increased —GlcNAcß1–6Man1–6Manß— branching in asparagine-linked oligosaccharides. Somatic mutations and drugs which block expression of the ß1–6 branched oligosaccharides are potent inhibitors of tumor cell invasion and metastasis in animal models. This suggests that the oligosaccharides are required for metastasis to occur and therefore their increased presence in primary tumors may be diagnostic of metastatic disease. Although antibodies to the ß1–6 branched portion of the oligosaccharides are not available, a plant lectin leukoagglutinin (L-PHA) has been shown to bind specifically to this structure.

L-PHA lectin histochemistry was performed on paraffin sections of human breast and colon tissues. All breast carcinomas and epithelial hyperplasia with atypia showed significantly increased L-PHA staining compared to fibroadenomas and hyperplasia without atypia. In histological sections of colon, adenomas showed a small but significant increase in L-PHA staining compared to normal colonic epithelium, while carcinomas showed greatly increased reactivity. In addition, Dukes stage C tumors showed higher levels of L-PHA staining than stage A tumors. These results demonstrate that L-PHA-reactive ß1–6 branched N-linked oligosaccharides are consistently increased in neoplasias of human breast and colon and that the level of L-PHA staining correlates with the pathological staging of the diseases.

¹ This work was supported by research grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Medical Research Council of Canada to J. W. Dennis, J. W. D. is a research scholar of the National Cancer Institute of Canada.

² To whom requests for reprints should be addressed, at Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.

Received 8/10/90. Accepted 10/25/90.

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