Impact of PARP-1 and DNA-PK expression on survival in patients with glioblastoma multiforme

Purpose: To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GEM) patients after postoperative radiotherapy. Materials and methods: Thirty four patients with GBM received postoperative radiotherapy. Tumor sections were examined for poly-ADP ribose polymerase-1 (PARP-1) and DNA protein kinase (DNA-PK) expression. Immunohistochemical staining intensities of PARP-1 and DNA-PK were determined (score 0-3) and expression levels were correlated with patients overall survival. Results: Median survival time of the whole study group was 10.0 months (95% CI 8.1-11.9). Median survival of patients with high and low (>= median and <median) tumor PARP-1 levels were 10.0 months (95% CI 7.9-12.1) and 12.0 months (95% CI 8.3-15.7), respectively (p = 0.93). In contrast, median survival of patients with high and low tumor DNA-PK levels were 9.0 months (95% CI 7.2-10.8) and 13.0 months (95% CI 10.7-15.3), respectively (p = 0.02). In multivariate analysis, DNA-PK expression emerged as a significant independent predictor for overall survival (HR 3.9, 95% CI 1.5-10.7, p = 0.01). Conclusion: This hypothesis generating study showed that high tumor levels of DNA-PK correlate with poor survival of GBM patients. Further studies are needed to confirm these results and to clarify whether DNA-PK inhibitors might have a potential to radiosensitize GBM and improve the treatment outcome of this devastating disease. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 101 (2011) 127-131