The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival.

PURPOSE

Malignant astrocytic gliomas, including anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), result from various genetic perturbations and dysregulated gene expression. Identifying genetic prognostic markers could be more useful for stratifying glioma patients than gross pathology alone.

EXPERIMENTAL DESIGN

cDNAs were generated by reverse transcriptase using mRNAs from gliomas and adjacent normal tissues from 86 patients. The tissues used for analysis were 45 AAs, 42 GBMs, and 7 samples of adjacent normal tissue. The levels of PAX6, PTEN, vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) gene expression were quantified using real-time quantitative reverse transcription-PCR and normalized to beta-actin. All statistical tests used were two-sided.

RESULTS

PAX6 expression was significantly reduced in GBM compared with AA (P < 0.0001). The relative levels of PTEN, EGFR, and VEGF expression also differed significantly among glioma grades. Multivariate Cox analysis of glioma samples, adjusting for patient age, histology, recurrent status, and levels of PTEN, EGFR, VEGF, and PAX6 (7 variables) showed a correlation between a low level of PAX6 expression in malignant astrocytic gliomas and unfavorable patient outcomes (hazard ratio, 0.34; 95% confidence interval, 0.18-0.63). Recursive partitioning analysis showed a favorable outcome for patients with high expression values of PTEN and PAX6 compared with low expression values of one or both genes (P < 0.0001).

CONCLUSION

The expression levels of PAX6, PTEN, and VEGF but not EGFR were independent prognostic markers, and the model including 7 variables was able to account for 55% of the variation in survival times for malignant astrocytic glioma patients.