Survivin is significantly overexpressed in esophageal cancers but does not predict intrinsic resistance

Survivin is a member of the inhibitor of apoptosis protein (IAP) gene family and is expressed in a variety of malignant tumors. Anti-sense targeting against survivin sensitized tumor cells to chemotherapy. We examined the potential of quantitative survivin mRNA expression to predict response or non-response to cis-platinum/5-FU based neoadjuvant radiochemotherapy (36 Gy) in 53 patients with locally advanced esophageal cancers (cT3/T4,Nx,M0). Tissue samples were collected by endoscopic biopsy prior to treatment. Total cellular RNA was isolated from biopsies and reverse-transcribed. In real-time quantitative PCR assays (TaqMan™) absolute survivin mRNA expression was determined in tumors (T) and normal tissues (N) and standardized for ß-actin. Relative survivin gene expression was defined as T/N ratio standardized for ß-actin. Absolute and relative gene expression levels were examined for correlation with the objective histomorphological response to neoadjuvant therapy. Histomoprhologic regression was defined as major response when tumor specimens contained less than 10% vital residual tumor cells or in case a pathologic complete response was obtained. All tumors were resected by transthoracic en bloc esophagectomy. Median survivin expression was 5.13 (min. 0, max. 611) in T and 2.35 (min. 0, max. 54) in N. Median relative survivin mRNA expression (T/N ratio) was 1.66 (min. 0, max. 97) and survivin expression was significantly higher in T than N (p < 0.0001, Wilcoxon, exact test) Absolute or relative survivin mRNA expression levels showed no association with either response or non-response to neoadjuvant therapy (cut-off values from ROC data according to Metz et al. 1973). Survivin mRNA is significantly overexpressed in locally advanced esophageal tumors compared to paired normal tissue. Overexpression however, was not associated with objective histomorphologic response or non-response and is not a suitable marker to predict intrinsic resistance or response to our treatment regime in esophageal cancer. This study is supported by the Marga and Walter Boll-Stiftung.