Significance of syndecan-1 expression in ductal carcinoma in situ of the breast.

BACKGROUND: Fibroblast growth factor-2 (FGF-2) supports tumor progression in breast cancer. FGF-2 signaling is modulated by heparan sulfate proteoglycans, such as syndecan-1 (CD138). The exact role of CD138 in ductal carcinoma in situ of the breast (DCIS) is still uncertain. Differential expression depending on grading could suggest a role for syndecan-1 during growth and tumor progression. MATERIALS AND METHODS: Samples of 127 cases of breast DCIS associated with follow-up data were included. CD138 staining intensity, number of positive cells, intracellular and tissue localization were examined. RESULTS: Median follow-up was 45.4 months and median recurrence-free survival (RFS) 86 months. Age, menopausal status and previous hormone replacement therapy had no significant influence on RFS. Smoking significantly influenced RFS (p=0.008). Endocrine therapy or radiotherapy did not improve RFS. Grading was not correlated with CD138 staining intensity, but was significantly associated with the percentage of CD138-positive cells (low-vs. high-grade, p=0.043). Estrogen receptor (ER) expression did not influence staining intensity of CD138 (p=0.247), but negatively correlated with the proportion of CD138-positive cells (p=0.032). Progesterone receptor (PR) expression significantly influenced the intensity of staining (p=0.010) and the percentage of CD138-positive cells (p=0.004); both were increased in PR-negative cases. CD138 staining intensity and percentage of positive cells did not correlate with RFS. Nuclear grade and syndecan-1 staining localization were significantly associated (p=0.001). ER-positive, and PR-positive DCIS more often exhibited membrane-bound syndecan-1 than ER- or PR-negative cases (p=0.001). Nuclear grade and tissue localization of CD138 correlated significantly (p=0.005). PR influenced CD138 tissue distribution, while ER did not. Syndecan-1 localization did not statistically impact RFS. CONCLUSION: In DCIS of different nuclear grades, tissue localization of syndecan-1 is significantly divergent, suggesting a specific effect on biology and progression of DCIS.

Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer.

In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC.