Analysis of p53 mutation and expression in pleomorphic xanthoastrocytoma

Abstract

Pleomorphic xanthoastrocytoma (PXA) is a rare, superficially situated tumor that most frequently occurs in the temporal lobe of young adults and is often associated with seizures. It generally has a relatively favorable prognosis. 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. 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. Of 55 primary PXAs, 35 (64%) showed staining in <1% of tumor cells, 15 (27%) in 1-10%, 4 (7%) in 11-50%, and only 1 (2%) in >50%. No significant increase in p53 protein expression was noted in recurrences, even when associated with increased histological anaplasia. We found a TP53 heterozygous mutation in exon 7 in 1 of 47 primary tumors that yielded useable DNA, and in its recurrence 3 years later. This tumor, a grade II PXA, did not show signs of anaplastic transformation at recurrence. Eleven additional recurrences from 7 patients, 5 of which showed signs of histological anaplasia, did not show TP53 mutations in exons 5-8. Based on our data, the p53 mutation appears to be an uncommon (2%) genetic event in PXA formation and does not appear to be involved in tumor progression. Consequently, our findings suggest that the genetic events that underlie PXA formation differ from those involved in diffuse astrocytoma.

Frequent loss of chromosome 9, homozygous CDKN2A/p14ARF/CDKN2B deletion and low TSC1 mRNA expression in pleomorphic xanthoastrocytomas

“…Comparative genomic hybridization (CGH) analysis of three PXAs detected gain on chromosome 7 and loss on 8p as recurrent imbalances (Yin et al, 2002). Molecular genetic studies revealed that mutations in the TP53 tumor-suppressor gene are restricted to a small fraction of cases (Paulus et al, 1996;Giannini et al, 2001;Kaulich et al, 2002). Thus, to date no specific genetic aberration has been linked to PXAs.…”

Anaplastic Pleomorphic Xanthoastrocytoma: Morphological and Molecular Features of Three Cases

“…Immunopositivity of neuronal markers such as synaptophysin, Class III beta tubulin, neurofilament protein had been reported [11] [12]. As an astrocytic marker, p53 is negative or focally positive [18]. Vu et al observed GFAP positivity in 22 cases, S-100 positivity in 11 cases, Neurofilament positivity in 7 of 13 tested cases, synaptophysin in 5 of 12 tested cases [17].…”

“…Interpretation and determination of the discriminating role of immunohistochemical stains is difficult regarding the existence of cases in the literature reported as immunonegative for neuronal and astrocytic markers. Giannini et al specifically suggested that p53 was strongly positive in GBM's and therefore this feature could be useful in differential diagnosis of APXA [18].…”

Anaplastic Pleomorphic Xanthoastrocytomas

“…In 2001, Giannini et al [44]published their analysis of p53 mutation and expression in 55 PXA cases. Of these, only 35 were typical PXAs, whereas the remaining 20 (36%) showed varying degrees of anaplastic changes.…”

“…Of these, only 35 were typical PXAs, whereas the remaining 20 (36%) showed varying degrees of anaplastic changes. Giannini et al [44]concluded that p53 mutation (2%) was an uncommon genetic event in PXA formation and probably not involved in tumor progression.…”