Survivin protein expression predicts poor outcome in patients with primary breast cancer

Abstract

547 Introduction: Survivin plays multiple roles in malignancy including inhibition of apoptosis, stimulation of proliferation and promotion of angiogenesis, and is up regulated in malignant tissues. Survivin is currently being investigated both as a target for new anticancer treatments and as a new tumor marker. The aim of this work was to study the expression and potential clinical value of survivin in breast cancer. Methods Survivin expression was measured by ELISA in primary breast cancer tissue extracts from 399 patients with a median clinical follow up of 48 months. Results Survivin levels were significantly increased in high grade compared to low grade tumors (p<0.001), in hormone receptor-negative compared to receptor-positive tumors (p=0.011), in HER-2 positive versus HER-2 negative tumors (p<0.047) and in VEGF-positive versus VEGF-negative tumors (p<0.0001). Using Spearman correlation analysis, survivin levels correlated weakly but significantly with numbers of nodal metastases (r=0.11, p=0.024, n=388), total VEGF levels (r=0.23, p<0.0001, n=386) and VEGF165 levels (r=0.23, p<0.0001, n=386). Using the median value as a cut-off point, high levels of survivin were associated with both shortened disease-free (Log Rank test p=0.014) and overall survival (Log Rank test p=0.015). When categorized using the 25th, 50th and 75th percentiles as cut-off points, survivin was an independent predictor of disease-free survival (p=0.037), i.e., patients with the highest quartile of survivin levels had a significantly shorter disease-free survival period than those with the lowest quartile. Conclusions We conclude that increased expression of survivin is associated with adverse outcome in patients with primary breast cancer. These patients with high levels of survivin are potential candidates for treatment with new anti-survivin (e.g, antisense oligonucleotides) therapies. No significant financial relationships to disclose.