PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
Authors: Hua-Bei Guo; Heather Johnson; Matthew Randolph; Tamas Nagy; Ryan Blalock; Michael Pierce Journal: Proc Natl Acad Sci U S A Date: 2010-11-15 Impact factor: 11.205
Authors: Yehia Mechref; Ahmed Hussein; Slavka Bekesova; Vitara Pungpapong; Min Zhang; Lacey E Dobrolecki; Robert J Hickey; Zane T Hammoud; Milos V Novotny Journal: J Proteome Res Date: 2009-06 Impact factor: 4.466
Authors: Petra B dos-Santos; Juliana S Zanetti; Gabriela S Vieira-de-Mello; Moacyr B M Rêgo; Alfredo Ribeiro-Silva A; Eduardo Isidoro Carneiro Beltrão Journal: Int J Clin Exp Pathol Date: 2014-04-15