Role of p53 gene mutation in tumor aggressiveness of intracranial meningiomas

Abstract

The mutations that occur in the p53 tumor suppressor gene have been studied in various human malignant tumors. However, little is known about this gene in meningiomas. To investigate the relationship and frequency of p53 gene mutations, the p53 polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) and immunohistochemical study were performed on the 41 intracranial meningiomas (21 benign, 11 atypical, and 9 malignant). The higher the p53 protein expression rate, the poorer the histologic grade (9.5%, 72.7%, and 88.9% in benign, atypical and malignant meningioma, respectively) (p=0.000). The p53 protein expression rate was higher in recurrent meningioma (71.4%) than in nonrecurrent meningioma (10.5%) (p=0.002). PCR-SSCP method was performed in positive p53 protein immunoreactivity cases. p53 gene mutation rate was higher in the atypical (62.5%) and malignant (25%) meningiomas than in the benign meningioma (0%) (p=0.232). Also, the rate was higher in recurrent menigioma (20%) than in nonrecurrent meningioma (0%) (o=0.495). Among five to eight exons of the p53 gene, the mutation was observed on exon 7 more frequently. In conclusion, p53 immunoreactivity and p53 gene mutation are closely correlated with histologic grade and histologic atypia of intracranial meningiomas. p53 gene mutation would be considered as a useful marker to detect the progression of intracranial meningiomas.

Assessment of candidate immunohistochemical prognostic markers of meningioma recurrence

“…Interestingly, the p53 LI and histoscore (but not the labelling intensity) has an inverse correlation with the chance of recurrence in the WHO grade I tumours in our study, but if we examine all the WHO grades, the increased staining in the higher grades, changes to forward proportion, similarly to prior studies [7,14,15]. This may be explained by the fact that the p53 immunoreactivity does not distinguish between the wild type (WT) and mutant protein; in non-recurrent cases increased normal protein may have a beneficial effect as p53 is involved in DNA damage repair.…”

“…The anticancer activity of p53 is through several mechanisms: it activates DNA repair proteins, induces growth arrest at the G1/S regulation point through p21 or initiates apoptosis if the DNA damage is irreversible [12]. It has been investigated also in meningioma and several studies showed a positive correlation with the grade and tumour recurrence [4,7,8,14,15,24,26], whereas authors reported the grade as an independent predictive factor of recurrences with high Mib1 and p53 LI being a supportive marker helpful in borderline cases [31].…”

“…It has been demonstrated that meningioma cells show positivity for PR; the ratio of the positive cells is inversely proportional to the WHO grade [18,27]. Also described earlier that the cellular biosynthesis of PR in meningioma is not oestrogen regulated as it is other sex steroid in tissues [5,7]. PR is encoded by the PGR gene on the long arm of chromosome 11.…”

Expression of ki-67 and p53 in meningiomas

“…Mutation of p53 gene results in metabolically stable abnormal protein that accumulates in the nucleus reaching the level to be easily detected by immunostains. Expression of p53 protein in tissue section is an indicator of possible mutation in p53 gene itself [10,11]. In the present study, we aimed to investigate the immunohisto-chemical profile of meningiomas by using Ki-67 and p53 as markers with established roles in tumor progression and to determine the association of these markers with histological grade and subtype.…”

Original article Poly(ADP-ribose) polymerase-1 (PARP1) and p53 labelling index correlates with tumour grade in meningiomas

“…The role of p53 has already been examined in the meningiomas: some of the examinations ended with negative or equivocal findings [43,[48][49][50], but some of them showed a significant correlation between the p53 status and the grade or recurrence of the tumour [4,7,8,19,20,28,37,41,44,46,57]. It is also described that p53 immunopositive cells are more frequent in the perinecrotic areas of post-embolised cases than in preserved parts of the tumour [39].…”