Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Epidermal growth factor receptor gene amplification as a prognostic marker in glioblastoma multiforme: results of a meta-analysis

MS Huncharek MD 1,2, B Kupelnick BA 2

1 Dept Clinical Oncology, Marshfield Clinic Cancer Center, Marshfield, WI, 2 Meta-Analysis Reserearch Group, Stevens Point, WI,

AIMS: Amplification of the epidermal growth factor receptor (EGFR) gene is considered a possible marker of poor prognosis in glioblastoma multiforme (GBM). This report presents the results of a meta-analysis of the available data addressing this issue. METHODS: Using previously described methods, a meta-analysis was designed to assess the possible prognostic importance of EGFR gene amplification in GBM. One-year survival data derived from seven published studies were analyzed using a general variance based method employing confidence intervals described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of death at one year from diagnosis associated with EGFR gene amplification positive versus negative disease. RESULTS: Prior to calculation of a RRs, an analysis for homogeneity (Q) showed Q to equal 9.21. With six degrees of freedom, this yielded a p value of 0.12 indicating that the data are homogenous and could be combined. Pooling all seven studies gave a RRs of 1.13 with a 95% confidence interval of 0.71-1.80, a non-statistically significant result. Possible sources of confounding were identified. CONCLUSIONS: The data suggest that EGFR amplification per se, cannot be considered a prognostic marker in GBM. Important potential confounding factors are the influence of underlying EGFR gene mutation on patient survival and lack of control for important known clinical prognostic indicators in many studies. Future work must incorporate these parameters in multi-variate analyses to determine whether EGFR gene alterations are truly associated with poor clinical outcome.

KEY WORDS: brain neoplasm, astrocytoma, survival, multivariate analysis.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on prognostic markers.