High syndecan‐1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis

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Abstract
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 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). 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% 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). 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. Cancer 2003;98:474–83. © 2003 American Cancer Society. DOI 10.1002/cncr.11515