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.