Revisiting the role of p53 in primary and secondary glioblastomas.
Glioblastoma multiforme (GBM) develops from astrocytes and is the most aggressive primary cancer in humans. Invading cells grow rapidly and form their own blood vessels making them difficult to surgically remove or treat. GBM may develop de novo (primary) or through progression from a low-grade or anaplastic astrocytoma (secondary). Mutational inactivation of the p53 gene and presence of aberrant p53 expression are reported in GBM, suggesting that p53 has a role in tumor progression. This study of seven de novo GBM and four secondary GBM patients, indicated that nine out of eleven (82%) had overexpression of p53. Our histopathological analysis showed that the expression of p53 in three out of four (75%) secondary GBM was confined to the nucleus and the p53 positive cells were randomly distributed throughout the tumor. The expression of p53 in four out of seven (57%) de novo GBM was cytoplasmic, diffusive, and confined to the perivascular region of the tumor. In two (29%) de novo samples both nuclear as well as cytoplasmic staining that was not confined to the perivascular area was observed. The results suggest that cytoplasmic p53 may contribute to the formation and maintenance of de novo GBM by virtue of its control of the vasculature of tumors. Furthermore, cytoplasmic p53 may reflect an association of p53 with Cullin 7, PARC, or with the sequestering partner of p53, mortalin. These results underscore the significance of p53 in the tumorigenesis of de novo GBM.
Nagpal
Julie
J
Department of Neurosurgery, New York Medical College, Valhalla, New York 10595, USA.
Jamoona
Amrith
A
Gulati
Nicholas D
ND
Mohan
Avinash
A
Braun
Alex
A
Murali
Raj
R
Jhanwar-Uniyal
Meena
M
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D006801:Humans; D008297:Male; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53