Objective: Syndecan-1 is a cell surface heparan sulphate proteoglycan which participates in cell proliferation, cell migration and cell-matrix interactions. Epithelial syndecan-1 expression is reduced in several malignant tumours, but in breast and pancreatic cancer, increased expression has also been described. Loss of epithelial syndecan-1 has been associated with poor prognosis in some forms of cancer, but previous findings in breast cancer have been contradictory. The objective of this study was to evaluate the prognostic value of the immunohistochemical expression of syndecan-1 in a series of 200 patients with invasive breast cancer with a median follow-up of 17 years. Methods: Formalin-fixed paraffin-embedded specimens were stained using a monoclonal antibody against syndecan-1. Results: Syndecan-1 was expressed in the epithelium in 61% and in the stroma in 67% of the tumours. Epithelial syndecan-1 expression was associated with negative oestrogen receptor (ER) status (p < 0.01), and stromal syndecan-1 expression with positive ER status (p = 0.02). The breast cancer-specific 10-year overall survival for patients with epithelial syndecan-1 expression was 65%, compared with 82% for those with loss of epithelial expression (p = 0.02). Ten-year survival was 66% for those expressing stromal syndecan-1 and 83% for those lacking stromal expression (p = 0.15). Patients with both epithelial and stromal expression had a 10-year survival of only 56%, compared to 78% in patients with other expression pattern combinations (p < 0.002). In Cox multivariate analysis, only axillary involvement and tumour size were significant predictors of breast cancer-specific survival. Conclusion: Concomitant expression of syndecan-1 in both epithelium and stroma may be a predictor of unfavourable prognosis in breast cancer, and in contrast with previous studies, loss of epithelial syndecan-1 was associated with a more favourable prognosis.

1.
Bernfield M, Kokenyesi R, Kato M, Hinkes MT, Spring J, Gallo RL, Lose EJ: Biology of the syndecans: A family of transmembrane heparan sulfate proteoglycans. Annu Rev Cell Biol 1992;8:365–393.
2.
Hayashi KM, Hayashi M, Jalkanen JH, Firestone RL, Trelstad M, Bernfield M: Immunocytochemistry of cell surface heparan sulfate proteoglycan in mouse tissues. A light and electron microscopic study. J Histochem Cytochem 1987;35:1079–1088.
3.
Matsumoto A, Ono M, Fujimoto Y, Gallo RL, Bernfield M, Kohgo Y: Reduced expression of syndecan-1 in human hepatocellular carcinoma with high metastatic potential. Int J Cancer 1997;74:482–491.
4.
Wiksten J-P, Lundin J, Nordling S, Lundin M, Kokkola A, von Boguslawski K, Haglund C: Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer. Int J Cancer 2001;95:1–6.
5.
Pulkkinen JO, Penttinen M, Jalkanen M, Klemi P, Grénman R: Syndecan-1:A new prognostic marker in laryngeal cancer. Acta Otolaryngol 1997;117:312–315.
6.
Inki P, Joensuu H, Grenman R, Klemi P, Jalkanen M: Association between syndecan-1 expression and clinical outcome in squamous cell carcinoma of the head and neck. Br J Cancer 1994;70:319–323.
7.
Nackaerts K, Verbeken E, Deneffe G, Vanderschueren B, Demedts M, David G: Heparan sulfate proteoglycan expression in human lung-cancer cells. Int J Cancer 1997;74:335–345.
8.
Kumar-Singh S, Jacobs W, Dhaene K, Weyn B, Bogers J, Weyler J, Van Marck E: Syndecan-1 expression in malignant mesothelioma: Correlation with cell differentiation, WT1 expression, and clinical outcome. J Pathol 1998;186:300–305.
9.
Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, Lander AD, Korc M: Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Cancer Res 2001;61:5562–5569.
10.
Conejo JR, Kleeff J, Koliopanos A, Matsuda K, Zhu ZW, Goecke H, Bicheng N, Zimmermann A, Korc M, Friess H, Büchler MW: Syndecan-1 expression is up-regulated in pancreatic but not in other gastrointestinal cancers. Int J Cancer 2000;88:12–20.
11.
Barbareschi M, Maisonneuve P, Aldovini D, Cangi MG, Pecciarini L, Angelo Mauri F, Veronese S, Caffo O, Lucenti A, Palma PD, Galligioni E, Doglioni C: High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer 2003;98:474–483.
12.
Hirabayashi K, Numa F, Suminami Y, Murakami A, Murakami T, Kato H: Altered proliferative and metastatic potential associated with increased expression of syndecan-1. Tumor Biol 1998;19:454–463.
13.
Stanely MJ, Stanley MW, Sanderson RD, Zera R: Syndecan-1 expression is induced in the stroma of infiltrating breast carcinoma. Am J Clin Pathol 1999;112:377–383.
14.
UICC: TNM Classification of Malignant Tumors, ed 4. Berlin, Springer, 1987.
15.
Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: Experience from a large study with long-term follow-up. Histopathology 1991;19:403–410.
16.
Hedley DW, Friedlander ML, Taylor IW, Rugg CA, Musgrove EA: Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. J Histochem Cytochem 1983;31:1333–1335.
17.
Baisch H, Göhde W, Linden WA: Analysis of PCP data to determine the fraction of cells in various phases of cell cycle. Radiat Environ Biophys 1975;12:31–39.
18.
Burbach BJ, Friedl A, Mundhenke C, Rapraeger AC: Syndecan-1 accumulates in lysosomes of poorly differentiated breast carcinoma cells. Matrix Biol 2003;22:163–177.
19.
Steinfeld R, Van Den Berghe H, David G: Stimulation of fibroblast growth factor receptor-1 occupancy and signaling by cell surface-associated syndecans and glypican. J Cell Biol 1996;133:405–416.
20.
Gallo R, Kim C, Kokenyesi R, Adzick NS, Bernfield M: Syndecans-1 and -4 are induced during wound repair of neonatal but not fetal skin. J Invest Dermatol 1996;107:676–683.
21.
Pumphrey CY, Theus AM, Li S, Parrish RS, Sanderson RD: Neoglycans, carbodiimide-modified glycosaminoglycans: A new class of anticancer agents that inhibit cancer cell proliferation and induce apoptosis. Cancer Res 2002;62:3722–3728.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.