Birc5 (Survivin) Is A Prognostic Biomarker And Potential Drug Target For Patients With Malignant Peripheral Nerve Sheath Tumors.

Abstract Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue cancer with high mortality, and there are currently few therapeutic options beyond surgery. We have performed a transcriptome study of 30 MPNSTs and 8 neurofibromas and used a tissue microarray (TMA) with cores from 63 MPNSTs to identify candidate genes and proteins for targeted therapy. The anti-apoptotic gene BIRC5 was one of the most significantly upregulated genes in MPNST vs neurofibroma. This gene is located on the long arm of chr 17, and we have previously shown common gains of 17q sequences and pinpointed BIRC5 as a potential target in MPNSTs. Recently BIRC5 was also identified as a potential drug target. Here, we show that MPNST patients with above median BIRC5 mRNA expression levels had significantly worse 5-year disease-specific survival (DSS: 26%) than patients with below median mRNA levels (DSS: 87%) (P=.0003). Immunohistochemical analyses showed that increased protein expression is also associated with a worse disease outcome (P=.02). We recently performed a meta-analysis on survival for NF1 associated MPNST and sporadic MPNST based on 1800 patients which suggest no difference between these groups. Our data suggest that MPNST patients who present tumors with high expression of BIRC5 might benefit from targeted treatment directed against BIRC5. Citation Format: Matthias Kolberg, Maren Høland, Trude H. Ågesen, Rolf I. Skotheim, Bodil Bjerkehagen, Kirsten S. Hall, Fredrik Mertens, Sigbjørn Smeland, Dina C. Lev, Ben Davidson, Ragnhild A. Lote. BIRC5 (Survivin) is a prognostic biomarker and potential drug target for patients with malignant peripheral nerve sheath tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-189. doi:10.1158/1538-7445.AM2013-LB-189