Primary (de novo) glioblastomas develop in older patients and are characterized by epidermal growth factor (EGF) receptor amplification/overexpression, p16 deletion, and PTEN mutations, whereas secondary glioblastomas that progressed from low-grade or anaplastic astrocytoma develop in younger patients and frequently contain p53 mutations.
The frequency of p53 mutations was 28.8% (19 of 66) and was higher in anaplastic astrocytoma (9 of 14, 64.3%,) than in glioblastoma multiforme (GBM; 7 of 27, 25.9%,), supporting previous speculation that there are at least two genetic pathways leading to GBM, a de novo pathway without p53 mutation and a "progressive" pathway with p53 mutation.
Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged survival, respectively.
PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.
Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged survival, respectively.
The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA.
In patients with multiple biopsies, methylation of the RB1 promoter was not detectable in the less malignant precursor lesions, ie, low-grade diffuse and anaplastic astrocytoma.
The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA.
We had previously reported that loss of heterozygosity (LOH) of the D17S379 locus on 17p13.3 was significantly more frequent in high-grade gliomas (anaplastic astrocytoma, AA; glioblastoma multiforme, GBM) than in those of a low-grade diffuse astrocytoma (DA); however, this was independent of alterations at the TP53 locus, We also showed that LOH of D17S379 was associated with positive staining for p53 protein on immunohistochemistry, but LOH of the TP53 gene had no such association.
The association of alterations in p53, MDM2, p16 or EGFR with the survival of patients with anaplastic astrocytoma or glioblastoma remains controversial.
However, the tumors formed by the cells expressing exogenous VEGF (121) or VEGF (165) retained the phenotype of AA, lacking areas of necrosis that are the hallmark of the GBM phenotype.
Complete lack of expression of TSC-22 occurred in one sample of anaplastic astrocytoma, as well as in meningioma, brain sarcoma, sarcomatous meningioma, and oligodendroglioma.
We analysed by RT-PCR the expression of mRNAs coding for the human variants of Gln transporters: ASCT2 (system ASC), SNAT1 [ATA1] (system A), SNAT3 [SN1] and SNAT5 [SN2] (system N), in samples of human malignant gliomas WHO grades III/IV (anaplastic astrocytoma and glioblastoma), glioma-derived cell cultures, brain metastases from peripheral organs, and control brain tissue.
We performed a pilot clinical trial of safety and effectiveness of this interferon beta gene therapy in five patients with malignant glioma (glioblastoma multiforme or anaplastic astrocytoma).
Although there was little difference in age of patient by EGFR amplification or expression among glioblastoma multiforme cases, EGFR gene amplification was associated with much older age of onset of anaplastic astrocytoma; for example, EGFR-amplified anaplastic astrocytoma cases were on average 63 years old compared with 48 years for nonamplified cases (P = 0.005).
We prepared polyclonal anti-survivin serum to establish a survivin index for stained sections, using an immunohistochemical procedure, according to the method used for scoring MIB-1 index, and then stained 29 paraffin-embedded sections from surgical specimens of 29 patients who were classified into three grades of World Health Organization with the mean age of low grade astocytoma (grade II) being 34.7; anaplastic astrocytoma (grade III), 48.8; and glioblastoma multiform (grade IV), 58.4.
We prepared polyclonal anti-survivin serum to establish a survivin index for stained sections, using an immunohistochemical procedure, according to the method used for scoring MIB-1 index, and then stained 29 paraffin-embedded sections from surgical specimens of 29 patients who were classified into three grades of World Health Organization with the mean age of low grade astocytoma (grade II) being 34.7; anaplastic astrocytoma (grade III), 48.8; and glioblastoma multiform (grade IV), 58.4.
The results of real-time quantitative reverse transcription-PCR analysis showed that cathepsin D transcript levels became significantly higher as the glioma grade advanced (P = 0.0466, glioblastoma and anaplastic astrocytoma; P = 0.0008, glioblastoma and astrocytoma; P = 0.0271, glioblastoma and normal brain tissue; unpaired t test).
Our data revealed that ASCL1 is overexpressed in progressive astrocytoma as evidenced by increased levels of ASCL1 transcripts in 85.71% (6/7) of grade II diffuse astrocytoma (DA), 90% (9/10) of grade III anaplastic astrocytoma (AA) and 87.5% (7/8) of secondary GBMs, while the majority of primary de novo GBMs expressed similar to or less than normal brain levels (66.67%; 8/12).
As we have found that Lyn, but not Fyn, activity promotes migration of glioblastoma cells in response to the cooperative signal generated by platelet-derived growth factor receptor beta and integrin alpha(v)beta3, we compared the activity and expression of Lyn and Fyn in glioblastoma (grade IV) tumor biopsy samples with that in anaplastic astrocytoma (grade III) tumors, nonneoplastic brain, and normal autopsy brain samples.