Prognostic molecular markers with no impact on decision-making: the paradox of gliomas based on a prospective study

Abstract

This study assessed the prognostic value of several markers involved in gliomagenesis, and compared it with that of other clinical and imaging markers already used. Four-hundred and sixteen adult patients with newly diagnosed glioma were included over a 3-year period and tumour suppressor genes, oncogenes, MGMT and hTERT expressions, losses of heterozygosity, as well as relevant clinical and imaging information were recorded. This prospective study was based on all adult gliomas. Analyses were performed on patient groups selected according to World Health Organization histoprognostic criteria and on the entire cohort. The endpoint was overall survival, estimated by the Kaplan-Meier method. Univariate analysis was followed by multivariate analysis according to a Cox model. p14(ARF), p16(INK4A) and PTEN expressions, and 10p 10q23, 10q26 and 13q LOH for the entire cohort, hTERT expression for high-grade tumours, EGFR for glioblastomas, 10q26 LOH for grade III tumours and anaplastic oligodendrogliomas were found to be correlated with overall survival on univariate analysis and age and grade on multivariate analysis only. This study confirms the prognostic value of several markers. However, the scattering of the values explained by tumour heterogeneity prevents their use in individual decision-making.

Figure 1

Relationship between p14ARF, p16 INK4A and PTEN expressions and Kaplan–Meier estimates of overall survival in the entire series. hTERT expression is correlated to overall survival in high-grade tumours, but not in the entire series.

Figure 2

Relationship between 10p15, 10q23, 10q26 and 13q LOH, and Kaplan–Meier estimates of overall survival.

Figure 3

Box-plots showing scattering of gene expression values, for low-grade (A) and high-grade (B) tumours, respectively.