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.

LOH on 10p14‐p15 targets the PFKFB3 gene locus in human glioblastomas

“…In the study of Schmidt et al (2002), a poor prognosis of patients with LOH on 10p12 (P ¼ 0.0287) was reported. Interestingly, LOH of the KLF6 locus in 10p14-p15 was not correlated with overall survival as shown by Wager et al (2008).…”

“…The association of survival with LOH on 10p was less pronounced. Wager et al (2008) demonstrated a correlation between 10p LOH and shorter survival in the overall cohort of gliomas but not in the fraction of glioblastomas (Wager et al, 2008). In the study of Schmidt et al (2002), a poor prognosis of patients with LOH on 10p12 (P ¼ 0.0287) was reported.…”

Genome-wide association study identifies five susceptibility loci for glioma

“…Although 5p15.33 copy number change is uncommon in glioblastoma multiforme (GBM; Supplementary Fig. 2a), TERT expression correlates with glioma grade and prognosis 16 . Several lines of evidence raise the possibility of a second locus defined by rs2853676, which also maps to intron 2 of TERT (1,341,547 bp; OR = 1.26, 95% CI: 1.20–1.32; P = 4.21 × 10 −14 ) and is in weak LD with rs2736100 ( D′ = 0.67 and r 2 = 0.15 and D′ = 0.81 and r 2 = 0.24 in HapMap and GWA scan, respectively).…”

Loss of heterozygosity on chromosome 10q in glioblastomas, and its association with other genetic alterations and survival in Indian patients

“…[11] More recently, Wager et al noted no association with overall survival for either PTEN or DMBT1. [36] In the present study, the mean overall survival period of patients with LOH 10q was 6.03 months while that of patients not showing LOH was 9.21 months. Survival rates were lower for patients with LOH 10q compared to those with retained heterozygosity [ Table 3, Figure 3].…”