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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Handerson
Tamara
T
Department of Pathology, University of Massachusetts School of Medicine, Worchester, Massachusetts, USA.
Camp
Robert
R
Harigopal
Malini
M
Rimm
David
D
Pawelek
John
J
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009844:Oligosaccharides / Q000032:analysis* / Q000737:chemistry; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome
D009844:Oligosaccharides