A study of clinico-pathological parameters and O⁶-methylguanine DNA methyltransferase (MGMT) promoter methylation status in the prognostication of gliosarcoma.
In conclusion, this study demonstrates that concomitant TMZ together with radiation therapy increases GSM-patient survival independent of MGMT promoter methylation.
The O6-methylguanine-DNA methyltransferase promoter methylation studies were significantly more frequent in the GBMs than GSMs (80.1% vs. 44.7%, P < 0.001).
In the present study, we determined the status of MGMT using methylation-specific polymerase chain reaction (PCR) and immunohistochemistry on paraffin-embedded specimens in 12 human gliosarcomas, and these results were then related to overall survival (OS) and response to alkylating agents.
We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.
Abnormalities identified by immunohistochemistry included p21 immunonegativity (60%, 25%, 93%), which was most frequent in TE-GBM (P = .008), strong nuclear p53 staining (29%, 29%, 41%), strong membranous staining for epidermal growth factor receptor (EGFR) (21%, 63%, 19%), which was most frequent in E-GBM (P = .03), and an increased frequency of p27 immunonegativity in gliosarcomas (15% negative, 85% focal) compared with tumors without sarcoma (38% strongly positive) (P = .009).
<b>Objective:</b> Gliosarcoma (GSC), a rare malignant brain tumor, is considered as a variant of isocitrate dehydrogenase 1 wild type (IDH1-WT) glioblastoma (GBM).
As mutations of the p53 tumor suppressor gene represent an early event in the development of gliomas, we attempted to determine whether both components of gliosarcomas share identical alterations of the p53 gene.
Single-strand conformation polymorphism followed by direct DNA sequencing revealed p53 mutations in five of 19 gliosarcomas (26%) and PTEN mutations in seven cases (37%).
We identified a subset of tumors (n = 18, 8.8% of high-grade gliomas) exhibiting moderate-to-strong immunoreactivity that enriched for the IDH-wild-type glioblastoma variants gliosarcoma (n = 10) and the newly described epithelioid glioblastoma (n = 4).
Both genes are induced in biologically and genetically heterogenous glioblastoma cell lines (LN-229, LN-Z308, U87MG, T98G), whereas, in gliosarcoma cells (D247MG), only the VEGF gene is induced.
Abnormalities identified by immunohistochemistry included p21 immunonegativity (60%, 25%, 93%), which was most frequent in TE-GBM (P = .008), strong nuclear p53 staining (29%, 29%, 41%), strong membranous staining for epidermal growth factor receptor (EGFR) (21%, 63%, 19%), which was most frequent in E-GBM (P = .03), and an increased frequency of p27 immunonegativity in gliosarcomas (15% negative, 85% focal) compared with tumors without sarcoma (38% strongly positive) (P = .009).
Gastrin significantly decreased the overall growth rate in the rat C6 and the human U373 high-grade astrocytic tumor models with either CCK(B) or CCK(C) gastrin receptor but not in the 9L rat gliosarcoma, which had no CCK(B) gastrin receptor (but had CCK(A) receptor) and only weak amounts of CCK(C) receptor.
The presence of the three CCK receptor subtypes was also assayed on three experimental models, i.e. the U373 human glioma, the C6 rat glioma and the 9L rat gliosarcoma.
Furthermore, Sox2 deficiency specifically impaired the astrocytic component of a biphasic gliosarcoma xenograft model while allowing the formation of tumors with sarcomatous phenotype.