1p19q LOH patterns and expression of p53 and Olig2 in gliomas: relation with histological types and prognosis

Abstract

In glial tumors, the loss of heterozygosity of the 1p and 19q chromosomal arms is thought to be a marker of good prognosis in oligodendroglial tumors. However, 1p and 19q loss of heterozygosity may be telomeric, interstitial, centromeric or affect the whole arm of the chromosome and the associations between these different patterns and tumor type, other molecular markers and patient prognosis remain unclear. We analyzed microsatellite markers in a region spanning the chromosome from the telomere to the centromere, to characterize the pattern of 1p and 19q loss of heterozygosity in 39 infiltrative gliomas, including astrocytomas, glioblastomas, oligoastrocytomas and oligodendrogliomas. We then studied the association between loss of heterozygosity and the expression of p53 protein and Olig2, as analyzed using immunohistochemistry, and epidermal growth factor receptor (EGFR) gene amplification, as investigated using fluorescence in situ hybridization (FISH). Finally, we assessed the influence of molecular markers on the overall survival of patients. We identified five different 1p19q loss of heterozygosity patterns among the tumors studied and found that loss of heterozygosity over the whole 1p arm was associated with loss of heterozygosity over the whole 19q arm in 90% of cases. 1p19q whole loss was present in all the classical oligodendrogliomas, whereas other 1p19q loss patterns predominated in oligoastrocytomas. 1p19q whole loss was also significantly associated with Olig2 overexpression, but was never observed in tumors overexpressing p53 protein. We also found that, among patients with contrast-enhancing tumors, those with 1p19q whole loss tended to survive for longer. In combination with classical histological and immunohistochemical data, 1p19q status determination provides pertinent information useful for (1) discriminating between histological types of gliomas and (2) identifying a subgroup of tumors that are associated with a better prognosis.

Alpha Internexin Expression Related with Molecular Characteristics in Adult Glioblastoma and Oligodendroglioma

“…The expression of proneural genes characterizes a group of malignant gliomas with a better prognosis than the "mesenchymal" subtype (26). In our study, the survival analysis based on 1p/19q codeletion and EGFR amplification status agreed with previously reported results (27, 28). …”

Alpha-internexin expression in gliomas: relationship with histological type and 1p, 19q, 10p and 10q status

“…This is consistent with other studies that report a significantly higher expression of INA in oligodendrogliomas than in glioblastomas and, in particular, in gliomas with 1p19q loss than in those with 1p19q retention 24 25 28 31 32. In our series, 1p19q wLOH was found in all typical oligodendrogliomas but never in other histological types, as we reported in a previous study6 and strong INA expression was directly related to 1p19q wLOH status. Inversely, all the tumours with a 10q wLOH status expressed little or no INA, whereas tumours with 10q retention showed either no, low or strong INA expression.…”

“…The combined whole loss of the 1p and 19q chromosomal arms, consisting of a whole 1p19q deletion corresponding to an unbalanced translocation t(1;19)(q10;p10)4 5 is a genomic alteration characteristically found in oligodendroglioma,6 and is associated with a good prognosis 7 8. The deletions of the 10p and 10q chromosome arms are most often reported in astrocytomas and glioblastomas, and are associated with a poor prognosis 2 9.…”

Integrated Genotypic Analysis of Hedgehog-Related Genes Identifies Subgroups of Keratocystic Odontogenic Tumor with Distinct Clinicopathological Features

“…LOHs at chromosome 1p and 9q are correlated with histological subtypes in glioma and medulloblastoma, respectively, and they can mold a histological and clinical phenotype [34], [35]. We speculated that the LOHs were correlated to the histological and clinical features of KCOT, and we checked this hypothesis.…”