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

Altered glycosylation of cell surface glycoproteins commonly accompanies malignant transformation. In rodent tumors, presence of larger N-linked oligosaccharides branched at the trimannosyl core is associated with the metastatic phenotype. In turn, drugs which inhibit branching of these complex-type N-linked oligosaccharides, e.g., swainsonine, block metastasis (1). Particular aberrant patterns of glycosylation can be used as markers for tumor progression, and lectins with known specificity are useful tools for probing such patterns. The lectin L-PHA 1 requires both galactose and the /31-6-1inked antenna for high affinity binding. Synthesis of the latter is dependent upon the activity of N-acetylglucosamine transferase V and favors the formation of poly-N-acetyllactosamine extensions, ultimately associated to the malignant phenotype. Following this rationale, Fernandes et al. (2) analyzed L-PHA reactivity in colon and breast cancer specimens at different pathological stagings. Malignant lesions were consistently more L-PHA reactive than their benign counterparts. Their findings prompted us to evaluate the prognostic value of L-PHA reactivity in breast cancer specimens. We analyzed 69 cases randomly taken from a series of 235 consecutive female patients with primary, nonmetastatic breast cancer admitted to the Mastology Department of the A. C. Camargo Hospital, S~o Paulo, Brazil, from January 1983 to December 1984, as described in a previous report from our group (3). L-PHA epithelial reactivity was evaluated by means of lectin histochemistry, as described by Fernandes et al. (2). Staining patterns were essentially the same as discussed in their paper. Tumors were either negative or positive for staining. The staining was diffuse cytoplasmic, sometimes concentrated in the Golgi area, or at the plasma membrane. Besides epithelial staining, stromal areas were also weakly positive, and this was more intense around epithelial cells. Vascular endothelial cells were consistently positive. L-PHA reactivity alone on epithelial cells was not significantly predictive of either disease-free interval or overall survival of these patients (Fig. 1). The most striking finding was the negative association between tumor L-PHA reactivity and the presence of axillary lymph node metastases at the time of diagnosis. Lymph node status is the most accurate predictor of long-term prognosis in breast cancer. Of the 50 patients with a L-PHA-positive tumor only 15 (30%) had lymph node involvement, whereas 11 of 19 (58%) L-PHA-negative tumors presented axillary metastasis (P = 0.0327, 9( 2 test). A similar finding was already suggested by Fernandes et aL as a trend in 12 cases. Despite that, the authors suggested a correlation with breast cancer progression, which was not observed on an epidemiological basis. Recently, an independent group had showed that L-PHA-binding oligosaccharides were unrelated to progression of mammary neoplasia in spontaneous and experimental metastasis models (4). Characterization of the glycoproteins which bear L-PHA-reactive oligosaccharides and an assessment of their functions might help explain the failure to ascribe a prognostic value for L-PHA reactivity in breast cancer. Dennis and Laferte (5) have shown previously that among the glycoproteins from human breast cancer tissue there are two major polypeptides which carry L-PHA-reactive oligosacchari-