Survivin: A potential predictive and prognostic marker in multimodal rectal cancer therapy.

Abstract

e14115 Background: Preoperative radiochemotherapy (RCT) is currently recommended in locally advanced rectal cancer with enhanced local control, higher sphincter preservation and decreased toxicity rates. Reliable predictive markers for an individualization of multimodal treatment are still lacking. We evaluated the intratumoral expression of survivin, an inhibitor of apoptosis, and its association with tumor regression parameters and prognosis in rectal cancer patients. Methods: 63 patients with stage II/III rectal cancers received multimodal treatment with curative surgery. 38 patients received preoperative RCT, 25 patients underwent primary surgery followed by adjuvant RCT. Nuclear and cytoplasmatic survivin expression were determined by immunhistochemistry in tumor biopsies and corresponding surgical specimens and were correlated with clinicopathologic parameters and survival. Results: In tumor biopsies, a high cytoplasmatic survivin expression correlated with advanced initial tumor stage (cT), whereas low survivin expression was associated with higher histomorphologic tumor regression after preoperative RCT. High survivin levels in surgical specimens were associated with advanced tumor stage in patients undergoing preoperative RCT, but not in patients after primary surgery. Preoperative RCT led to a significant down-regulation of intratumoral nuclear and cytoplasmatic survivin expression. Survivin down-regulation significantly correlated with RCT-induced reduction of tumor stage. However, comparing tumor biopsy and surgical specimen a deficient down-regulation of survivin was associated with an increased incidence of local recurrence. Conclusions: Our findings suggest that cytoplasmatic survivin expression in rectal cancer might be useful for response prediction to preoperative RCT and as a prognostic marker within multimodal treatment conceptions. Further investigations in a larger number of patients have to be initiated to validate these results. No significant financial relationships to disclose.