Baba Füsun, Swartz Kathryn, van Buren Regina, Eickhoff Jens, Zhang Yong, Wolberg William, Friedl Andreas
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA.
Breast Cancer Res Treat. 2006 Jul;98(1):91-8. doi: 10.1007/s10549-005-9135-2. Epub 2006 Apr 25.
Members of the syndecan and glypican families of cell surface heparan sulfate proteoglycans (HSPGs) are modulators of growth factor signaling and cell adhesion. Both loss and gain in expression of syndecans and glypicans has been associated with malignant progression. The goal of this project was to investigate a possible relationship between expression of cell surface HSPGs (syndecan-1, syndecan-4 and glypican-1) and established prognostic factors or clinical outcome in breast carcinomas. Tissue arrays containing 207 human breast carcinoma samples in duplicate were immuno-labeled with antibodies to syndecan-1, syndecan-4, glypican-1, Ki67, E-cadherin, estrogen receptor (ER) and progesterone receptor (PR). Clinical follow-up information was available for up to 18.6 years (median follow-up 6.2 years). Syndecan-1 and syndecan-4 expression in carcinoma cells ranged from complete loss to high expression, but glypican-1 was detected only in a small subset of breast carcinomas. Expression of all three HSPGs was significantly associated with the Ki67 proliferation index (syndecan-1: p=0.0025; syndecan-4: p<0.0001; glypican-1 p=0.01). Syndecan-1 and syndecan-4 expression correlated with ER negativity, grade, and size of the primary tumors. Syndecan-1 expression (but not syndecan-4 nor glypican-1) predicted patient outcome (DFS: p=0.0054; OS: p=0.0086). However, multivariate analysis failed to identify syndecan-1 as an independent prognostic marker, which was due to its significant association with established prognostic factors. The strong association between cell surface HSPGs and the Ki67 proliferation marker would support a biologic role in carcinoma growth regulation. Furthermore, the close correlation between syndecan expression and negative ER status raises the possibility of hormonal regulation or more likely an association with an aggressive, ER-negative carcinoma phenotype.
细胞表面硫酸乙酰肝素蛋白聚糖（HSPG）的syndecan和glypican家族成员是生长因子信号传导和细胞黏附的调节剂。syndecan和glypican表达的缺失和增加均与恶性进展相关。本项目的目的是研究细胞表面HSPG（syndecan-1、syndecan-4和glypican-1）的表达与乳腺癌既定预后因素或临床结局之间的可能关系。对包含207份人类乳腺癌样本复制品的组织芯片用抗syndecan-1、syndecan-4、glypican-1、Ki67、E-钙黏蛋白、雌激素受体（ER）和孕激素受体（PR）的抗体进行免疫标记。可获得长达18.6年的临床随访信息（中位随访时间6.2年）。癌细胞中syndecan-1和syndecan-4的表达范围从完全缺失到高表达，但glypican-1仅在一小部分乳腺癌中检测到。所有三种HSPG的表达均与Ki67增殖指数显著相关（syndecan-1：p = 0.0025；syndecan-4：p < 0.0001；glypican-1 p = 0.01）。syndecan-1和syndecan-4的表达与ER阴性、分级和原发肿瘤大小相关。syndecan-1的表达（而非syndecan-4和glypican-1）可预测患者结局（无病生存期：p = 0.0054；总生存期：p = 0.0086）。然而，多变量分析未能将syndecan-1鉴定为独立的预后标志物，这是由于其与既定预后因素的显著关联。细胞表面HSPG与Ki67增殖标志物之间的强关联将支持其在癌生长调节中的生物学作用。此外，syndecan表达与ER阴性状态之间的密切相关性增加了激素调节的可能性，或者更可能是与侵袭性ER阴性癌表型相关。
