Single-strand conformation polymorphism analysis of p53 exons 5-8 revealed migration shifts in two cases, one primary PXA without recurrence and one recurrent grade II PXA in which the primary tumor did not show a shift.
In the present study, we performed immunostaining for p53 protein and examined the mutation status of exons 5-8 of the p53 gene in 55 PXAs, 8 of which had undergone one or multiple recurrences.
We suggest that the incidence of TP53 mutations in pleomorphic xanthoastrocytoma may be underestimated and that molecular approaches should be used for greater diagnostic precision.
On sequencing of the 2 components separately after microdissection, both showed identical IDH1 R132H and TP53R273C point mutations, whereas the BRAF V600E mutation was limited to the PXA-like component.
The efficacy of bevacizumab, temozolomide, lomustine (CCNU), irinotecan (CPT 11), a tyrosine kinase inhibitor (sorafenib), a selective MEK1/2 inhibitor (cobimetinib), and a BRAF inhibitor (vemurafenib) were assessed in two subcutaneous xenografts: D645 PXA (V600E-mutant) and D2363 PXA (V600E-non-mutant) (n = 5-10 mice).
The BRAFV600E mutation occurs frequently in certain brain tumors such as pleomorphic xanthoastrocytoma, ganglioglioma, and pilocytic astrocytoma, and less frequently in epithelioid and giant cell glioblastoma.
Some glial-neuronal tumors (GNT) (pleomorphic xantho-astrocytoma [PXA], ganglioglioma [GG]) display BRAF-V600E mutation, which represents a diagnostic clue to these entities.
The ability of the polio: rhinovirus recombinant, PVSRIPO, to infect PXA (645 [BRAFV600E mutation], 2363) and medulloblastoma (D283, D341) cells were determined by viral propagation measurement and cell proliferation.
Both components were positive for the mutant IDH1 R132H and showed loss of ATRX expression, whereas BRAFV600E was restricted to the PXA-like component.
We evaluated the immunohistochemical (IHC) detection of BRAFV600E mutation in PXA by comparing to gold standard molecular analysis and investigating the interobserver variability of the IHC scoring.
In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8<sup>+</sup> tumor-infiltrating lymphocytes, and longer survival with the addition of BEV.
Prognostic significance of histological anaplasia and BRAFV600E mutation were retrospectively evaluated in 74 patients with pleomorphic xanthoastrocytoma (PXA).
In summary, we showed that PLGG tumorigenicity was low despite the presence of putative CSCs, and our data supported GFAP<sup>-</sup>/Vimentin<sup>+</sup> cells, <i>CDKN2A</i> homozygous deletion in trisomy chromosome 9 cells, and <i>BRAF V600E</i> mutation as candidate drivers of tumor progression in the PXA xenografts.
Although this glioma was difficult to clarify, diagnosis of pleomorphic xanthoastrocytoma with anaplastic feature was suggested based on the association of some pathological feature (eosinophilic granular bodies, reticulin network and diffuse CD34 expression) and the BRAFV600E mutation.
Our data indicate, that in addition to the histological and immunohistochemical evaluation, investigation of MGMT promoter methylation and in particular BRAFV600E mutations represent reliable additional tools to sustain differentiation of gcGBM from PXA on a molecular basis.