Beta1,6-branched oligosaccharides are increased in lymph node metastases and predict poor outcome in breast carcinoma

This study was designed to provide a comprehensive assessment on the role of beta1,6-branched oligosaccharides in the metastasis and outcome of breast carcinoma. Generation of these structures on N-glycans is initiated by beta1,6-N-acetylglucosaminyltransferase V and used by both myeloid cells and c...

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Bibliographic Details
Published in:Clinical cancer research 2005-04, Vol.11 (8), p.2969-2973
Main Authors: Handerson, Tamara, Camp, Robert, Harigopal, Malini, Rimm, David, Pawelek, John
Format: Article
Language:English
Subjects:
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Breast Neoplasms - therapy
Disease-Free Survival
Female
Humans
Lymph Nodes - chemistry
Lymph Nodes - pathology
Lymphatic Metastasis
Middle Aged
Multivariate Analysis
Oligosaccharides - analysis
Oligosaccharides - chemistry
Predictive Value of Tests
Prognosis
Treatment Outcome
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Summary:This study was designed to provide a comprehensive assessment on the role of beta1,6-branched oligosaccharides in the metastasis and outcome of breast carcinoma. Generation of these structures on N-glycans is initiated by beta1,6-N-acetylglucosaminyltransferase V and used by both myeloid cells and cancer cells in systemic migration. Tissue microarrays of >700 tumors (>400 patients; 30-year follow-up data) were stained through lectin histochemistry with leukocytic phytohemagglutinin (LPHA), a selective marker for beta1,6-branched oligosaccharides. Node-negative and node-positive primary tumors and patient-matched lymph node metastases were scored by blinded observers. Metastases stained at significantly greater intensities than did the patient-matched primary tumors (P < 0.0001), demonstrating for the first time that the abundance of beta1,6-branched oligosaccharides was directly associated with breast carcinoma nodal metastasis. Multivariate analyses revealed that beta1,6-branched oligosaccharides in primary tumors were a predictor of poor outcome, most notably in node-negative tumors, where an LPHA staining score of 3+ gave a risk factor of 3.3, independent of tumor size, nuclear grade, or patient age (P = 0.007). The data firmly establish a role for beta1,6-N-acetylglucosaminyltransferase V activity and beta1,6-branched oligosaccharides in breast carcinoma metastasis, and reemphasize the involvement, although poorly understood, of aberrant glycosylation in tumor progression.
ISSN:1078-0432