Association of survivin expression following neoadjuvant radiochemotherapy in rectal cancer with distant metastases and survival.

Abstract

483 Background: Valid molecular markers need to be implemented in clinical trials to fulfill the demand of a risk-adapted and more individualized multimodal therapy of locally advanced primary rectal cancer. In the present study the expression of the inhibitor-of-apoptosis (IAP) protein Survivin was evaluated in pre-treatment biopsies and corresponding post-treatment resection specimens, and was correlated to histo-pathological tumor characteristics and clinical follow-up. Methods: 116 patients with stage II/III rectal cancer treated with 5-FU-based neoadjuvant radiochemotherapy (RCT) within the German Rectal Cancer Trials were investigated. Survivin expression in pre-treatment biopsies and surgical resection specimens were determined by immunohistochemistry by two independent institutions and correlated with histopathologic parameters, tumor recurrences, disease-free and overall cancer-specific survival. Results: In pre-treatment biopsies, a higher Survivin expression correlated with advanced ypT (p=0.026) and ypUICC (p=0.05) stage as well as decreased disease-free survival (p=0.038) after preoperative RCT. High post-treatment Survivin levels were associated with advanced ypT stage (p=0.03) and residual lymph node metastases (p=0.04). Moreover, neoadjuvant RCT resulted in a significant down-regulation of Survivin expression (p < 0.0001). A failure of RCT-induced down-regulation was associated with development of distant metastases (p=0.0056) and cancer-related death (p=0.026), and was significantly correlated with disease-free (p=0.011*/0.02**) and cancer-specific survival (p=0.0017*/0.01**) in uni*- and multivariate** analyses. Conclusions: Survivin expression displays a marker with prognostic validity in rectal cancers. These results underline the usefulness of Survivin to monitor individual response to RCT in rectal cancer, and encourage anti-Survivin strategies in multimodal rectal cancer therapy within future randomised clinical trials. No significant financial relationships to disclose.