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The Expression of PAX6, PTEN, Vascular Endothelial Growth Factor, and
Epidermal Growth Factor Receptor in Gliomas. Relationship to Tumor Grade and Survival
Yi-Hong Zhou, Fang Tan, Kenneth R. Hess
and W. K. Alfred Yung
Departments of Neuro-Oncology [Y-H. Z., F. T., W. K. A.
Y.*]
and Biostatistics [K. R. H.], The University of Texas M. D. Anderson Cancer
Center, Houston, Texas 77030. *To whom requests for reprints should be addressed, at Department
of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center,
1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 745-1285;
Fax: (713) 745-4999; E-mail: wyung@mdanderson.org.
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 ß-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.
© 2003 American
Association for Cancer Research
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