Results suggested that aberrations of the p53 gene were not correlated with the malignancy of some types of brain tumors such as anaplastic astrocytoma and glioblastoma, contrary to previous observations on colorectal cancers.
The more malignant histological features of anaplastic astrocytoma and glioblastoma multiforme appear to be reflected by a greater incidence of p53 accumulation.
In experiments to identify molecules that might be important in the pathogenesis of glioblastoma multiforme, the most common malignant brain tumor, we found that annexin II (Lipocortin 2, p36), a likely second messenger in several different mitogenic pathways, was highly expressed in tumor tissue of glioblastoma multiforme (9 of 9) and highly anaplastic astrocytoma (2 of 6), but not in astrocytomas of lower pathological grade (0 of 6).
When p53 alterations is seen as an indicator for different pathogenic pathways in glioma formation, this study gives evidence for a difference between anaplastic astrocytoma and glioblastoma.
We studied the frequency of p53 immunoreactivity and gene alteration in 21 children with malignant astrocytomas (anaplastic astrocytoma and glioblastoma multiforme) and analysed the survival of patients with p53 immunoreactive versus non-reactive tumors.
Progression of low-grade astrocytomas to anaplastic astrocytoma or glioblastoma occurred at a similar frequency in lesions with (79%) and without (63%) p53 mutations (P = 0.32), indicating that this genetic alteration is associated with tumor recurrence but not predictive of progression to a more malignant phenotype.
To elucidate the role of gemistocytes in astrocytoma progression, we assessed the fraction of neoplastic gemistocytes, bcl-2 expression, p53 mutations, p53 immunoreactivity (PAb 1801), and proliferative activity (MIB-1) in 40 low-grade astrocytomas (World Health Organization (WHO) Grade II) with histologically proven progression to anaplastic astrocytoma (WHC Grade III) or glioblastoma (WHO Grade IV).
In a case of AA with a heterogenous microscopic appearance, heterozygosity of D17S379 was lost only in the area with a more malignant histology while both areas had no LOH or mutation of p53.
To elucidate the role of gemistocytes in astrocytoma progression, we assessed the fraction of neoplastic gemistocytes, bcl-2 expression, p53 mutations, p53 immunoreactivity (PAb 1801), and proliferative activity (MIB-1) in 40 low-grade astrocytomas (World Health Organization (WHO) Grade II) with histologically proven progression to anaplastic astrocytoma (WHC Grade III) or glioblastoma (WHO Grade IV).
To elucidate the role of gemistocytes in astrocytoma progression, we assessed the fraction of neoplastic gemistocytes, bcl-2 expression, p53 mutations, p53 immunoreactivity (PAb 1801), and proliferative activity (MIB-1) in 40 low-grade astrocytomas (World Health Organization (WHO) Grade II) with histologically proven progression to anaplastic astrocytoma (WHC Grade III) or glioblastoma (WHO Grade IV).
Kaplan-Meier survival estimation demonstrated that immunohistochemical positivity for mdm2 protein in patients with anaplastic astrocytoma or with glioblastoma multiforme was associated with a shorter survival time (p = 0.02).
Gemistocytes showed a significantly higher bcl-2 expression than all tumor cells, with a mean bcl-2 1 of 15.6% versus 2.7% in low-grade astrocytomas (p = 0.0004), 20.9% versus 3.0% in anaplastic astrocytoma (p = 0.002), and 30.2% versus 5.2% in glioblastomas (p = 0.0002).
The MIB-1 labelling index and the frequency and intensity of p53 staining in both the pilocytic astrocytoma and the astrocytoma group were significantly lower than in the anaplastic astrocytoma plus glioblastoma group (P < 0.001).
The MIB-1 labelling index and the frequency and intensity of p53 staining in both the pilocytic astrocytoma and the astrocytoma group were significantly lower than in the anaplastic astrocytoma plus glioblastoma group (P < 0.001).
The MIB-1 labelling index and the frequency and intensity of p53 staining in both the pilocytic astrocytoma and the astrocytoma group were significantly lower than in the anaplastic astrocytoma plus glioblastoma group (P < 0.001).
Amplification and overexpression of GAC1 was demonstrated in two of eight tumors where amplifications were previously evidenced by comparative genomic hybridization (one glioblastoma multiforme and one anaplastic astrocytoma), and in one of eight unselected glioblastomas multiforme.
Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma.