PURPOSE: To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GBM) 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. Copyright Â
PURPOSE: To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GBM) 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) tumorPARP-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 tumorDNA-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. Copyright Â
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