Barbareschi Mattia, Maisonneuve Patrick, Aldovini Daniela, Cangi Maria Giulia, Pecciarini Lorenza, Angelo Mauri Francesco, Veronese Silvio, Caffo Orazio, Lucenti Antonio, Palma Paolo Dalla, Galligioni Enzo, Doglioni Claudio
Department of Pathology, Santa Chiara Hospital, Trento, Italy.
Cancer. 2003 Aug 1;98(3):474-83. doi: 10.1002/cncr.11515.
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.
Specimens from 254 consecutive breast carcinoma (BC) cases (110 N0, 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).
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% CI, 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).
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.
Syndecan-1是一种跨膜硫酸乙酰肝素蛋白聚糖，参与细胞间粘附、细胞-基质粘附的组织以及生长因子信号传导的调节。
对254例连续的乳腺癌（BC）病例（110例N0，144例N1/2）的标本进行长期随访（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，已知c-erbB-2状态。还对20份乳腺组织样本（10对正常和肿瘤样本）评估了Syndecan-1 mRNA和蛋白表达。
106例（42%）BC中Syndecan-1高水平表达；逆转录聚合酶链反应（RT-PCR）研究证实了Syndecan-1上调。Syndecan-1高表达与高组织学分级、肿瘤大尺寸、高有丝分裂计数、c-erbB-2过表达以及ER和PgR阴性状态相关。单变量生存分析显示Syndecan过表达与预后不良相关（总生存（OS）和无病生存均P<0.01）。双变量生存分析显示Syndecan-1和c-erbB-2过表达有相加的不良影响。多变量分析时，Syndecan-1过表达与不良OS独立相关（风险比[HR]，1.71；95%置信区间[CI]，1.08-2.69）。在102例ER阴性患者组中，Syndecan-1高表达对OS也有独立的预后价值（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高表达仅在接受环磷酰胺-甲氨蝶呤-氟尿嘧啶方案治疗的患者中与更高的死亡风险相关（HR，1.9；P = 0.09）；对OS进行多变量分析时，这种关联具有独立的统计学意义（P = 0.03；HR，2.15）。
Syndecan-1在相当比例的乳腺癌中高水平表达，与侵袭性表型和不良临床行为相关。
