The results of immunohistochemistry are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III).
Real-time quantitative reverse transcriptase-polymerase chain reaction analysis showed that AM mRNA was correlated to the tumor type and grade, with high expression in all glioblastomas analyzed, whereas a low expression was found in anaplastic astrocytomas and barely detectable levels in low-grade astrocytomas and oligodendrogliomas.
Furthermore, screening with a defined threshold identified 6 genes that were highly expressed in GBM, including AFF2, CACNA2D3 and ARPP21, while the 6 highly expressed genes in OD notably included CNTN2.
Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n =27), and the degree of methylation correlated with low levels of AJAP1 expression (P = 0.045).
Whereas a mutation was not detected in the coding region of the SHREW1 gene in oligodendrogliomas, restoration of SHREW1 expression resulted in suppression of cell adhesion and migration.
Whereas a mutation was not detected in the coding region of the SHREW1 gene in oligodendrogliomas, restoration of SHREW1 expression resulted in suppression of cell adhesion and migration.
We additionally implanted 13 tumors to investigate the relationship between PI3K/AKT/mTOR pathway alterations and oligodendroglioma xenograft formation.
In WHO grade II-IV astrocytomas, CARPs were associated with molecular events related to more benign behavior, which was the case with CARP VIII in oligodendrogliomas and oligoastrocytomas as well.
In addition, nuclear staining of annexin-1 in oligodendroglial tumor cells was significantly reduced (P=0.0002), which may be used as a diagnostic tool for differentiating between astrocytomas and oligodendrogliomas.
The expression of the rPTP beta/zeta protein in oligodendrogliomas and astrocytomas was further validated by immunohistochemistry in an independent set of tumors.
However, no somatic mutations in APC were found among 91 neuroepithelial tumors (medulloblastoma, glioblastoma, astrocytoma, and oligodendroglioma), whether sporadic or associated with TS.
To determine whether p73 is involved in nonastrocytic brain tumour development, we analysed 65 tumour samples including 26 oligodendrogliomas, 4 ependymomas, 5 medulloblastomas, 10 meningiomas, 2 meningeal haemangiopericytomas, 2 neurofibrosarcomas, 3 primary lymphomas, 8 schwannomas and 5 metastatic tumours to the brain, for p73 alterations.
A total of 124 of 160 glioma samples (77.5%) displayed CpG island hypermethylation of both p73, p21 genes associated with the loss of mRNA expression (P < 0.001) and the loss of protein expressions (p53 independent p21 expression). p73 gene showed increased methylation frequency in all grades, 40 of 60 (66%) glioblastomas and 16 of 30 (53.3%) anaplastic astrocytoma, 10 of 20(50%) oligodendrogliomas, 8 of 20 (40%) ependymoma, and low-grade glioma 6 of 20 (30%).
Thus far, mutation analysis has provided no evidence for involvement of p73 in oligodendrogliomas, lung carcinoma, oesophageal carcinoma, prostatic carcinoma and hepatocellular carcinoma.
To determine whether p73 is a potential tumor suppressor gene involved in the development of oligodendrogliomas, we performed mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions.
The p73 gene encodes a protein structurally and functionally homologous to TP53, and maps to chromosomal band 1p36.33, where loss of heterozygosity has been observed in up to 90% of oligodendrogliomas and in 10-25% of diffuse astrocytomas.
Abnormal expression of peroxiredoxin 6 and rho GDP dissociation inhibitor alpha may be associated with malignant transformation in oligodendroglioma and these proteins might be candidates of molecular predictive factors.
Furthermore, screening with a defined threshold identified 6 genes that were highly expressed in GBM, including AFF2, CACNA2D3 and ARPP21, while the 6 highly expressed genes in OD notably included CNTN2.
Among the oligodendroglial lineage markers (Olig2, Sox10, ASCL1, and NKX2-2), ASCL1 and NKX2-2 displayed significantly different immunostaining between oligodendrogliomas and astrocytomas (p = 0.017 and 0.004, respectively), but none clearly differentiated between the 2 glial populations of oligoastrocytomas.