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

Mattia Barbareschi, Patrick Maisonneuve, Daniela Aldovini, Maria Giulia Cangi, Lorenza Pecciarini, Francesco Angelo Mauri, Silvio Veronese, Orazio Caffo, Antonio Lucenti, Paolo Dalia Palma, Enzo Galligioni, Claudio Doglioni

Research output: Contribution to journalArticle

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 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% 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.

Original languageEnglish
Pages (from-to)474-483
Number of pages10
JournalCancer
Volume98
Issue number3
DOIs
Publication statusPublished - Aug 1 2003

Keywords

  • Breast
  • Carcinoma
  • CD138
  • Immunohistochemistry
  • Prognosis
  • Syndecan-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Barbareschi, M., Maisonneuve, P., Aldovini, D., Cangi, M. G., Pecciarini, L., Mauri, F. A., Veronese, S., Caffo, O., Lucenti, A., Palma, P. D., Galligioni, E., & Doglioni, C. (2003). High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer, 98(3), 474-483. https://doi.org/10.1002/cncr.11515