Progression in Human Breast and Colon Neoplasia 6 Branched Oligosaccharides as a Marker of Tumor

Malignant transformation of murine and human cells is commonly associated with increased —GlcNAcffl-6Manal-6Manff— branching in asparagine-linked Oligosaccharides. Somatic mutations and drugs which block expression of the ,/l 6 branched Oligosaccharides are potent inhib itors 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 diag nostic of metastatic disease. Although antibodies to the 0\-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 histolÃ3g ica! sections of colon, adenomas showed a small but significant increase in L-PHA staining compared to normal colonie epithelium, while carci nomas 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/31-6 branched /V-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.