Recently, somatic mutations of the NF2 gene have been identified in sporadic meningiomas, thus supporting the hypothesis that the NF2 gene is also important in meningioma pathogenesis.
An increase in transcription was observed with the addition of promegestone (R5020), a progesterone agonist, only in meningioma cell cultures that were expressing the progesterone receptor.
Our results indicate that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. p53 immunoreactivity, even in the absence of detectable gene mutation, is also associated with atypia and does not appear in regular benign meningiomas.
Logistic regression analysis showed GSTT1 null and CYP2D6 poor metabolizer were risk factors in astrocytoma (odds ratio = 2.67 P = 0.0005 and odds ratio = 4.17 P = 0.0043, respectively) and meningioma (odds ratio = 4.52, P = 0.0001 and odds ratio = 4.90, P = 0.0132, respectively) when corrected for the other variables.
In this study, eight meningioma cell cultures were transiently transfected with a construct that contains two palindromic progesterone/glucocorticoid response elements in front of the thymidine kinase promoter and the chloramphenicol acetyl sequence of the tyrosine aminotransferase gene.
Logistic regression analysis showed GSTT1 null and CYP2D6 poor metabolizer were risk factors in astrocytoma (odds ratio = 2.67 P = 0.0005 and odds ratio = 4.17 P = 0.0043, respectively) and meningioma (odds ratio = 4.52, P = 0.0001 and odds ratio = 4.90, P = 0.0132, respectively) when corrected for the other variables.
These data show that both the progesterone and the glucocorticoid receptor in meningiomas are functional and support the concept that progestins and glucocorticoids may play an important role in meningioma growth.
These results are compatible with the hypothesis that the NF2 gene acts as a tumor suppressor and that its inactivation is important in the pathogenesis of sporadic meningioma.
To investigate this hypothesis, 31 meningioma specimens were subjected to Northern blot analysis, hybridization with a complementary DNA VEGF probe, and laser densitometry to determine the relative levels of VEGF mRNA expression.
mac25, a retinoic acid-inducible gene that is expressed at high levels in senescent epithelial cells, was initially cloned as a gene that is differentially expressed in meningioma.
We used Western blot analysis to examine the level of expression of the mdm2 and p53 proteins in a series of sixteen primary meningiomas and four meningioma cell lines.
We screened human primary and recurrent malignant glioma, juvenile pilocytic astrocytoma, medulloblastoma, and meningioma tissue specimens for alterations in p16 gene structure.