Detection of TP53 gene mutation in human meningiomas: A study using immunohistochemistry, polymerase chain reaction/single‐strand conformation polymorphism and dna sequencing techniques on paraffin‐embedded samples

Abstract

Mutations in the TP53 tumor suppressor gene have been studied in different types of brain tumors. Little is known about this genetic event in human meningioma, a mostly benign tumor. To investigate the frequency of TP53 gene mutations in human tumors derived from meningeal tissues, paraffin-embedded tissues from 30 cases (including 2 malignant and 4 atypical meningiomas, as well as 2 hemangioblastomas and 3 hemangiopericytomas) were screened by immunohistochemistry. Polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and direct DNA sequencing were thereafter performed in selected cases. Nuclear p53 staining was not seen in any of the 19 benign meningiomas tested, while atypical meningiomas, hemangioblastomas, and hemangiopericytomas displayed nuclear staining in a subpopulation of tumor cells in 4 out of 5, 2 out of 2, and 3 out of 3 cases, respectively. One malignant meningioma showed an intense nuclear staining and a band shift in SSCP. In this case, we identified a mutation in the TP53 gene at codon 161 changing GCC to ACC and resulting in an alteration of alanine to threonine in this position. Our results indicate that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. p53 immunoreactivity, even in the absence of detectable gene mutation, is also associated with atypia and does not appear in regular benign meningiomas.

Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: Toward a genetic model of meningioma progression

“…Absence of TP53 gene mutations in meningiomas has also been reported by Ohgaki et al (54) and single meningiomas with TP53 mutation have been found by other authors (55). Unless there are mutations in the rarely affected regions of TP53, alterations of this gene appear to be of minor significance in meningiomas.…”

Expression of Minichromosome Maintenance MCM6 Protein in Meningiomas is Strongly Correlated With Histologic Grade and Clinical Outcome

“…33 TP53 mutations or deletions were reported in atypical and anaplastic meningiomas, with a frequency ranging from 0% to 62%; however, grade I meningioma was not affected. 4,10,27,52,55 Nevertheless, there is considerable variability among the different studies. Amatya et al 4 did not find any mutation of TP53, despite a high frequency of p53 protein expression, thus suggesting that p53 protein is wild type.…”

Expression of hypoxia inducible factor-1α in tumors of patients with glioblastoma multiforme and transitional meningioma

“…Although the function of p53 is still not well understood, many lines of evidence indicate that meningiomas have low levels of p53, leading to speculations that p53 mutations may be involved in the etiology of these tumors. [54][55][56] It has been demonstrated that wildtype p53 promotes degradation of HIF-1a 57 so it may be expected that inactivation of p53 either results from somatic mutations or from functional inactivation, which would lead to increased HIF-1a expression in meningiomas. If functional p53 is lost, the proapoptotic effect of HIF-1a is lost and tumor progression is stimulated by HIF-1a via induction of angiogenesis.…”