β1,6-Branched oligosaccharides are increased in lymph node metastases and predict poor outcome in breast carcinoma
β1,6-Branched oligosaccharides are increased in lymph node metastases and predict poor outcome in breast carcinoma
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DOI：
10.1158/1078-0432.ccr-04-2211
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发表时间：
2005-04-15
影响因子：
11.5
通讯作者：
Pawelek, J
中科院分区：
文献类型：
--
作者：
Handerson, T;Camp, R;Pawelek, J
目的：本研究旨在全面评价β-1，6-支链寡糖在乳腺癌转移和预后中的作用。N-糖链上这些结构的产生是由β1，6-N-乙酰氨基葡萄糖转移酶V启动的，并被髓系细胞和癌细胞在全身迁移中使用。实验设计：通过凝集素组织化学和白细胞植物血凝素(LPHA)组织化学染色，对>；700肿瘤(>；400名患者；30年随访数据)进行染色，LPHA是1，6-分支寡糖的选择标记物。结果：转移性肿瘤的染色强度明显高于患者匹配的原发性肿瘤(P<；0.0001)，首次证实了β1，6-分支寡糖的丰富与乳腺癌的淋巴结转移直接相关。多变量分析显示，原发肿瘤中的β1，6-分支低聚糖是预后不良的预测因子，尤其是在淋巴结阴性的肿瘤中，LPHA染色评分为3+的风险系数为3.3，与肿瘤大小、核级别或患者年龄无关(P=0.007)。结论：这些数据证实了β1，6-N-乙酰氨基葡萄糖基转移酶V活性和β1，6-分支低聚糖在乳腺癌转移中的作用，并再次强调了异常糖基化在肿瘤进展中的作用，尽管了解较少。
Purpose: This study was designed to provide a comprehensive assessment on the role of beta 1,6-branched oligosaccharides in the metastasis and outcome of breast carcinoma. Generation of these structures on N-glycans is initiated by beta 1, 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 1,6-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 beta 1,6-branched oligosaccharides was directly associated with breast carcinoma nodal metastasis. Multivariate analyses revealed that beta 1,6-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 beta 1,6-N-acetylglucosaminyltransferase V activity and beta 1,6-branched oligosaccharides in breast carcinoma metastasis, and reemphasize the involvement, although poorly understood, of aberrant glycosylation in tumor progression.