High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis
High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis
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DOI：
10.1002/cncr.11515
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发表时间：
2003-08-01
期刊：
影响因子：
6.2
通讯作者：
Doglioni, C
中科院分区：
文献类型：
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作者：
Barbareschi, M;Maisonneuve, P;Doglioni, C
背景Syndecan-1是一种跨膜硫酸乙酰肝素蛋白多糖，参与细胞-细胞粘附、细胞-基质粘附的组织化和生长因子信号的调节。对254例连续乳腺癌（BC）病例（110例NO，144例N1/2）进行长期随访（中位数，95个月），对syndecan-1、雌激素受体（ER）、孕激素受体（PgR）和p53进行免疫染色;在154例病例中，c-erbB-2状态已知。还在20个乳腺组织样本（10个正常和肿瘤对）中评估了Syndecan-1 mRNA和蛋白表达。syndecan-1在106（42%）BC高水平表达; syndecan-1上调证实了逆转录-聚合酶链反应（RT-PCR）研究。syndecan-1的高表达与高组织学分级、大肿瘤大小、高核分裂计数、c-erbB-2过表达以及ER和PgR阴性状态相关。在单变量生存分析中，syndecan过表达与不良预后相关（总生存期（OS）和无病生存期均P < 0.01）。双变量生存分析显示syndecan-1和c-erbB-2过表达的副作用。在多变量分析中，syndecan-1过表达与OS差独立相关（风险比[HR]，1.71; 95%置信区间[CI]，1.08-2.69）。在102例ER阴性患者中，syndecan-1高表达对OS具有独立的预后价值（HR，2.42; 95%CI，1.21-4.82）。根据给予的辅助治疗类型对患者进行分层，syndecan-1的高表达仅与接受环磷酰胺-甲氨蝶呤-氟尿嘧啶方案治疗的患者的死亡风险较高相关（HR，1.9; P = 0.09）;在OS的多变量分析中，这种相关性被证明具有独立的统计学意义（P = 0.03; HR，2.15）。Syndecan-1在相当大比例的乳腺癌中以高水平表达，并且与侵袭性表型和不良临床行为相关。(C)2003年美国癌症协会。
BACKGROUND. Syndecan-1 is a transmembrane heparan sulphate proteoglycan that is involved in cell-cell adhesion, organization of cell-matrix adhesion, and regulation of growth factor signaling.METHODS. Specimens from 254 consecutive breast carcinoma (BC) cases (110 NO, 144 N1/2) with long-term follow-up (median, 95 months) were immunostained for syndecan-1, estrogen receptor (ER), progesterone receptor (PgR), and p53; in 154 cases, c-erbB-2 status was known. Syndecan-1 mRNA and protein expression also were evaluated in 20 breast tissue samples (10 normal and tumor pairs).RESULTS. Syndecan-1 was expressed at high levels in 106 (42%) BCs; syndecan-1 up-regulation was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) studies. High syndecan-1 expression was associated with high histologic grade, large tumor size, high mitotic count, c-erbB-2 overexpression, and ER and PgR negative status. At univariate survival analysis syndecan overexpression was related to poor prognosis (P < 0.01 for both overall survival (OS) and disease-free survival). Bivariate survival analysis showed an additive adverse effect for syndecan-1 and c-erbB-2 overexpression. At multivariate analysis, syndecan-1 overexpression was independently associated with poor OS (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.08-2.69). High syndecan-1 expression also was of independent prognostic value for OS in the group of 102 ER-negative patients (HR, 2.42; 95% Cl, 1.21-4.82). Stratifying patients on the basis of the type of adjuvant therapy given, high syndecan-1 expression was associated with a higher risk of death only in patients treated with the cyclophosphamide-methotrexate-fluorouracil regimen (HR, 1.9; P = 0.09); at multivariate analysis for OS, this association proved to be of independent statistical significance (P = 0.03; HR, 2.15).CONCLUSIONS. Syndecan-1 is expressed at high levels in a significant percentage of breast carcinomas and is related to an aggressive phenotype and poor clinical behavior. (C) 2003 American Cancer Society.