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High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis
Article first published online: 13 JUN 2003
Copyright © 2003 American Cancer Society
Volume 98, Issue 3, pages 474–483, 1 August 2003
How to Cite
Barbareschi, M., Maisonneuve, P., Aldovini, D., Cangi, M. G., Pecciarini, L., Angelo Mauri, F., Veronese, S., Caffo, O., Lucenti, A., Palma, P. D., Galligioni, E. and Doglioni, C. (2003), High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer, 98: 474–483. doi: 10.1002/cncr.11515
- Issue published online: 18 JUL 2003
- Article first published online: 13 JUN 2003
- Manuscript Accepted: 8 APR 2003
- Manuscript Revised: 29 MAR 2003
- Manuscript Received: 29 JAN 2003
- Associazione Italiana Ricerca Cancro (AIRC)
- Associazione Artigiani e Piccole Impresse
- Lega Italiana per la Lotta ai Tumori Sezione di Trento—Progetto Per L'Oncologia In Trentino
- Italian Ministry of Health, Ricerca Finalizzata 2002–2004
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. Cancer 2003;98:474–83. © 2003 American Cancer Society.