Breast Cancer Research and Treatment

, Volume 98, Issue 1, pp 91–98 | Cite as

Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype

  • Füsun Baba
  • Kathryn Swartz
  • Regina van Buren
  • Jens Eickhoff
  • Yong Zhang
  • William Wolberg
  • Andreas Friedl
Preclinical study

Summary

Members of the syndecan and glypican families of cell surface heparan sulfate proteoglycans (HSPGs) are modulators of growth factor signaling and cell adhesion. Both loss and gain in expression of syndecans and glypicans has been associated with malignant progression. The goal of this project was to investigate a possible relationship between expression of cell surface HSPGs (syndecan-1, syndecan-4 and glypican-1) and established prognostic factors or clinical outcome in breast carcinomas. Tissue arrays containing 207 human breast carcinoma samples in duplicate were immuno-labeled with antibodies to syndecan-1, syndecan-4, glypican-1, Ki67, E-cadherin, estrogen receptor (ER) and progesterone receptor (PR). Clinical follow-up information was available for up to 18.6 years (median follow-up 6.2 years). Syndecan-1 and syndecan-4 expression in carcinoma cells ranged from complete loss to high expression, but glypican-1 was detected only in a small subset of breast carcinomas. Expression of all three HSPGs was significantly associated with the Ki67 proliferation index (syndecan-1: p=0.0025; syndecan-4: p<0.0001; glypican-1 p=0.01). Syndecan-1 and syndecan-4 expression correlated with ER negativity, grade, and size of the primary tumors. Syndecan-1 expression (but not syndecan-4 nor glypican-1) predicted patient outcome (DFS: p=0.0054; OS: p=0.0086). However, multivariate analysis failed to identify syndecan-1 as an independent prognostic marker, which was due to its significant association with established prognostic factors. The strong association between cell surface HSPGs and the Ki67 proliferation marker would support a biologic role in carcinoma growth regulation. Furthermore, the close correlation between syndecan expression and negative ER status raises the possibility of hormonal regulation or more likely an association with an aggressive, ER-negative carcinoma phenotype.

Keywords

breast neoplasm cell adhesion receptors glypican growth factor receptors proteoglycan syndecan 

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Notes

Acknowledgements

Satoshi Kinoshita is acknowledged for his technical assistance in producing the tissue arrays and Sally Drew for performing the immunohistochemical stains. We also thank Dr. Caroline Alexander for helpful discussions. This work was in part funded by grants from the Susan G. Komen Foundation (BCTR0402969) and the␣National institutes of Health (R01-CA107012). The funding sources did not influence the study design. The departmental translational research initiative in pathology (TRIP lab) also contributed to this study.

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Füsun Baba
    • 1
    • 4
  • Kathryn Swartz
    • 1
  • Regina van Buren
    • 1
  • Jens Eickhoff
    • 2
  • Yong Zhang
    • 1
  • William Wolberg
    • 3
  • Andreas Friedl
    • 1
  1. 1.Department of Pathology and Laboratory MedicineUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of Biostatistics and Medical Informatics University of Wisconsin-MadisonMadisonUSA
  3. 3.Department of SurgeryUniversity of Wisconsin-MadisonMadisonUSA
  4. 4.School of MedicineHarran UniversitySanliurfaTurkey

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