Impact of genotype and morphology on the prognosis of glioblastoma

Abstract

The recognition of molecular subsets among glioblastomas has raised the question whether distinct mutations in glioblastoma-associated genes may serve as prognostic markers. The present study on glioblastomas (GBM) from 97 consecutively sampled adult patients is based on a clinical, histopathological, immunohistochemical, and molecular genetic analysis. Parameters assessed were age at diagnosis, survival, cell type, proliferation, necrosis, microvascular proliferation, sarcomatous growth, lymphocytic infiltration, thromboses, calcifications, GFAP expression, MIB-1 index, loss of heterozygosity (LOH) of the chromosomal arms 1p, 10p, 10q, 17p, 19q and structural alterations in the TP53, EGFR and PTEN genes. As in previous studies, younger age was significantly associated with better survival. Among the molecular parameters, TP53 mutations and LOH10q emerged as favorable and poor prognostic factors, respectively. TP53 mutations were a favorable prognostic factor independent of whether glioblastomas were primary or secondary. LOH1p or 19q, lesions suspected to be over-represented in long term survivors with malignant glioma, were not associated with better survival. However, the combination of LOH1p and LOH19q defined GBM patients with a significantly better survival. Notably, these patients did not exhibit morphological features reminiscent of oligodendroglioma. These findings indicate that genotyping of glioblastoma may provide clinical information of prognostic importance.