The observed global checkpoint signaling, in contrast to only focal areas of overabundant p53 (indicative of p53 mutation) in grade II astrocytomas, are consistent with DDR activation being an early event in gliomagenesis, initially limiting cell proliferation (low Ki-67 index) and selecting for mutations of p53 and likely other genes that allow escape (higher Ki-67 index) from the checkpoint and facilitate tumor progression.
However, there is only anecdotal information about MGMT methylation status and TP53 mutations during progression of low-grade diffuse astrocytoma (AII) to anaplastic astrocytoma (AIII) and secondary glioblastoma (sGB).
We conclude that, although TP53 mutations are detectable in a substantial fraction of WHO grade II astrocytomas, they do not appear to play a role in the malignant progression of these tumors and they are not of prognostic significance.
Prior studies have shown that TP53 mutations may occur in up to 25% of PXAs, suggesting that PXA may have an etiology similar to diffuse astrocytoma rather than pilocytic astrocytoma.
Expression of estrogen receptors, androgen receptor and steroid receptor coactivator-3 is negatively correlated to the differentiation of astrocytic tumors.
Expression of estrogen receptors, androgen receptor and steroid receptor coactivator-3 is negatively correlated to the differentiation of astrocytic tumors.
Unusual findings include: TP53 mutation in a juvenile pilocytic astrocytoma; TP53 and PTEN mutations in a de novo glioblastoma, a gliosarcoma with identical mutations in gliomatous and sarcomatous components, and an infratentorial anaplastic astrocytoma with an earlier supratentorial grade II astrocytoma bearing the same TP53 mutation but not the PTEN mutation or loss of heterozygosity (LOH) of 10q23.
TP53 mutations are frequent and early events in the pathogenesis of WHO grade II astrocytomas/oligoastrocytomas, and most of the univariately detected overall prognostic impact of the TP53 status must be related to the influence of the gemistocytic subtype.
We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review.
We retrospectively reviewed the characteristics of 40 IDH-wildtype TERTp-mutant astrocytomas (grade II n = 19, grade III n = 21) and compared them to those of 114 IDH-mutant lower grade gliomas (LGG), of 92 IDH-wildtype TERTp-mutant glioblastomas, and of 15 IDH-wildtype TERTp-wildtype astrocytomas.
The majority of glioblastomas develop rapidly with a short clinical history (primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress from diffuse astrocytoma or anaplastic astrocytoma.
Significant differences in the median overall survival were observed in astrocytoma patients grouped on the basis of the presence of IDH1 mutation: survival was 24 months longer in grade II astrocytoma and 12 months longer in glioblastoma.